3,3'-Diindolylmethane and indole-3-carbinol: potential therapeutic molecules for cancer chemoprevention and treatment via regulating cellular signaling pathways.

Dietary compounds in cancer prevention have gained significant consideration as a viable method. Indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) are heterocyclic and bioactive chemicals found in cruciferous vegetables like broccoli, cauliflower, cabbage, and brussels sprouts. They are synthesized after glycolysis from the glucosinolate structure. Clinical and preclinical trials have evaluated the pharmacokinetic/pharmacodynamic, effectiveness, antioxidant, cancer-preventing (cervical dysplasia, prostate cancer, breast cancer), and anti-tumor activities of I3C and DIM involved with polyphenolic derivatives created in the digestion showing promising results. However, the exact mechanism by which they exert anti-cancer and apoptosis-inducing properties has yet to be entirely understood. Via this study, we update the existing knowledge of the state of anti-cancer investigation concerning I3C and DIM chemicals. We have also summarized; (i) the recent advancements in the use of I3C/DIM as therapeutic molecules since they represent potentially appealing anti-cancer agents, (ii) the available literature on the I3C and DIM characterization, and the challenges related to pharmacologic properties such as low solubility, and poor bioavailability, (iii) the synthesis and semi-synthetic derivatives, (iv) the mechanism of anti-tumor action in vitro/in vivo, (v) the action in cellular signaling pathways related to the regulation of apoptosis and anoikis as well as the cell cycle progression and cell proliferation such as peroxisome proliferator-activated receptor and PPARγ agonists; SR13668, Akt inhibitor, cyclins regulation, ER-dependent-independent pathways, and their current medical applications, to recognize research opportunities to potentially use these compounds instead chemotherapeutic synthetic drugs.

GC/MS chemical profiling and isolation of secondary metabolites from Leontice ewersmannii.

GC/MS chemical profiling of the aerial parts of Leontice ewersmannii revealed the presence of various bioactive compounds of which 20 compounds were in n-hexane fraction and 3 compounds in basic DCM fraction. Among the identified compounds alkaloids, fatty acids and their esters, fatty alcohols, hydrocarbons, and sterol were detected. Phytochemical investigation of the aerial parts of L. ewersmannii led to isolation of 17 compounds including 1-heptacosanol (1), phytol (2), lupenone (3), palmitic acid (4), oleic acid (5), stigmasterol (6), stigmast-7-en-3-ol (7), methyl palmitate (8), methyl linoleate (9), butyl palmitate (10), butyl linoleate (11), dimethyl dodecanedioate (12), methyl cerebronate (13), ß-sitosterol (14), ß-sitosterol 3-O-ß-glucopyranoside (15), sophoridine (16) and camoensine (17). The structures of the isolated compounds were determined by 1D NMR, HR-ESI-MS, and GC-MS. All methyl esters of fatty acids are possible artifacts during extraction. Additionally, the antimicrobial activity of the total extract and different fractions was screened, and they exhibited no inhibition of the growth at the tested concentration ranging from 8 to 200 µg/mL.

Paclitaxel and its semi-synthetic derivatives: comprehensive insights into chemical structure, mechanisms of action, and anticancer properties.

Cancer is a disease that can cause abnormal cell growth and can spread throughout the body. It is among the most significant causes of death worldwide, resulting in approx. 10 million deaths annually. Many synthetic anticancer drugs are available, but they often come with side effects and can interact negatively with other medications. Additionally, many chemotherapy drugs used for cancer treatment can develop resistance and harm normal cells, leading to dose-limiting side effects. As a result, finding effective cancer treatments and developing new drugs remains a significant challenge. However, plants are a potent source of natural products with the potential for cancer treatment. These biologically active compounds may be the basis for enhanced or less toxic derivatives. Herbal medicines/phytomedicines, or plant-based drugs, are becoming more popular in treating complicated diseases like cancer due to their effectiveness and are a particularly attractive option due to their affordability, availability, and lack of serious side effects. They have broad applicability and therapeutic efficacy, which has spurred scientific research into their potential as anticancer agents. This review focuses on Paclitaxel (PTX), a plant-based drug derived from Taxus sp., and its ability to treat specific tumors. PTX and its derivatives are effective against various cancer cell lines. Researchers can use this detailed information to develop effective and affordable treatments for cancer.

Nutritional Sources and Anticancer Potential of Phenethyl Isothiocyanate: Molecular Mechanisms and Therapeutic Insights.

Phenethyl isothiocyanate (PEITC), a compound derived from cruciferous vegetables, has garnered attention for its anticancer properties. This review synthesizes existing research on PEITC, focusing on its mechanisms of action in combatting cancer. PEITC has been found to be effective against various cancer types, such as breast, prostate, lung, colon, and pancreatic cancers. Its anticancer activities are mediated through several mechanisms, including the induction of apoptosis (programmed cell death), inhibition of cell proliferation, suppression of angiogenesis (formation of new blood vessels that feed tumors), and reduction of metastasis (spread of cancer cells to new areas). PEITC targets crucial cellular signaling pathways involved in cancer progression, notably the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB), Protein Kinase B (Akt), and Mitogen-Activated Protein Kinase (MAPK) pathways. These findings suggest PEITC's potential as a therapeutic agent against cancer. However, further research is necessary to determine the optimal dosage, understand its bioavailability, and assess potential side effects. This will be crucial for developing PEITC-based treatments that are both effective and safe for clinical use in cancer therapy.

Enhancing chemical and physical stability of pharmaceuticals using freeze-thaw method: challenges and opportunities for process optimization through quality by design approach.

The freeze-thaw (F/T) method is commonly employed during the processing and handling of drug substances to enhance their chemical and physical stability and obtain pharmaceutical applications such as hydrogels, emulsions, and nanosystems (e.g., supramolecular complexes of cyclodextrins and liposomes). Using F/T in manufacturing hydrogels successfully prevents the need for toxic cross-linking agents; moreover, their use promotes a concentrated product and better stability in emulsions. However, the use of F/T in these applications is limited by their characteristics (e.g., porosity, flexibility, swelling capacity, drug loading, and drug release capacity), which depend on the optimization of process conditions and the kind and ratio of polymers, temperature, time, and the number of cycles that involve high physical stress that could change properties associated to quality attributes. Therefore, is necessary the optimization of F/T conditions and variables. The current research regarding F/T is focused on enhancing the formulations, the process, and the use of this method in pharmaceutical, clinical, and biological areas. The present review aims to discuss different studies related to the impact and effects of the F/T process on the physical, mechanical, and chemical properties (porosity, swelling capacity) of diverse pharmaceutical applications with an emphasis on their formulation properties, the method and variables used, as well as challenges and opportunities in developing. Finally, we review the experimental approach for choosing the standard variables studied in the F/T method applying the systematic methodology of quality by design.

Component Composition and Biological Activity of Various Extracts of Onosma gmelinii (Boraginaceae).

Onosma roots are widely used in traditional medicine to treat various diseases throughout the world. In this study, for the first time, we investigated the component composition and biological activity of various extracts from the roots of Onosma gmelinii collected in the highlands of the Kakpakty Mountains of the Almaty region (Republic of Kazakhstan). Extracts were obtained by three different methods: percolation extraction, ultrasound-assisted extraction, and supercritical carbon dioxide extraction. The component composition of the extracts was determined by gas chromatography/mass spectrometry (GC/MS), naphthoquinones by thin-layer chromatography (TLC), and spectrophotometric method. In this study, the presence of shikonin and its derivatives in the extracts was confirmed. The concentration of naphthoquinones during CO2 extraction was about 40%, during ultrasonic extraction about 3%, and during percolation extraction about 1.3%. The GC-MS method identified 69 chemical compounds in the ultrasonic extract, 46 compounds in the CO2 extract, and 51 compounds in the percolation extract. The extracts were tested on a panel of bacteria and viruses: two Gram-negative bacteria (Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 9027); nine Gram-positive bacteria (Staphylococcus aureus ATCC 6538-P, Staphylococcus aureus ATCC BAA-39, Staphylococcus epidermidis ATCC 51625, Staphylococcus epidermidis ATCC 12228, Streptococcus pyogenes ATCC 19615, Streptococcus pneumoniae ATCC BAA-660, Enterococcus hirae ATCC 10541, Enterococcus faecalis ATCC 51575, Enterococcus faecium ATCC 700221); and two fungal species (Candida albicans ATCC 10231, Candida albicans ATCC 2091); five subtypes of influenza virus A (A/FPV/Weybridge/78 (H7N7), A/Swine/Iowa/15/30 (H1N1), A/black-headed gull/Atyrau/743/04 (H13N6), A/FPV/Rostock/1934 (H7N1), A/Almaty/8/98 (H3N2)). The root extracts of Onosma gmelinii showed antibacterial activity in different degrees against all tested Gram-positive bacterial strains, while no inhibitory effect on Gram-negative bacteria was observed. The results indicated that the ultrasonic extract effectively inhibits the growth of the majority of tested Gram-positive bacteria (MBC from 18.3 to 293.0 µg/mL). CO2 extract had the greatest bactericidal activity (MBC from 0.1 to 24.4 µg/mL). Percolation extract insignificantly inhibited bacterial growth (MBC from 2343.8 to 4687.5 µg/mL). CO2 extract and ultrasonic extract significantly reduced the activity of C. albicans. The results of the antiviral action showed that the ultrasonic extract has the greatest effectiveness against different subtypes of the influenza virus A, while other extracts did not show significant activity.

Phytochemical constituents and antioxidant activity of Echinops albicaulis.

Two thiophenes; 5-(3-buten-1-ynyl)-2,2'-bithiophene (2) and α-tertthienyl (9), two alkaloids; echinopsine (10) and echinorine (11), three flavonoids; genkwanin (5), apigenin (6), and rutin (7), two triterpenoids; lupeol acetate (1) and lupeol linoleate (4), together with 2,6,10-trimethyldodeca-2,6,10-triene (4) and ß-sitosterol glucoside (8) were isolated from the aerial parts of Echinops albicaulis. Antioxidant, antimicrobial and antiprotozoal activities were evaluated. E. albicaulis aqueous methanolic extract (50, 10, and 1 mg/mL) showed significant antioxidant activity comparable to the potent antioxidant, N-acetyl cysteine, moreover, the aqueous methanolic extract (1 mg/mL) significantly reduced intracellular reactive oxygen species in active cell cultures of human peripheral blood mononuclear cells under oxidative stress more than the reference antioxidant N-acetyl cysteine. None of the isolated compounds showed antimicrobial or antiprotozoal activities at concentration up to 20 µg/mL.