Salvurmin A and Salvurmin B, Two Ursane Triterpenoids of Salvia urmiensis Induce Apoptosis and Cell Cycle Arrest in Human Lung Carcinoma Cells

Background: Ursane triterpenoids could be considered as novel multi-target therapeutic anti-cancer agents. Salvurmin A and Salvurmin B are novel cytotoxic ursane triterpenoids isolated from the aerial parts of Salvia urmiensis, an endemic plant species of Iran. Methods: In this study, we assessed cytotoxicity of these compounds against two human cancer cell lines and one human normal cell line and investigated its mechanism via apoptosis and cell cycle arrest. Results: Salvurmin A and B showed the most cytotoxic effect on A549 cells compared to other studied cancer cells. IC50 values for Salvurmin A and B against A549 cells were 35.6 ± 1.5 and 19.2 ± 0.8 µM, respectively. Based on annexin V staining, both of these compounds significantly induced apoptosis in A549 cells. Moreover, these two compounds significantly increased cell accumulation in G2/M and decreased the number of cells in G0/G1 phases in A549 cells in a dose-dependent manner. Conclusion: Based on the results Salvurmin B can be considered as potential candidate for further studies against human lung carcinoma

Neuropharmacological Potential of Diterpenoid Alkaloids

This study provides a narrative review of diterpenoid alkaloids (DAs), a family of extremely important natural products found predominantly in some species of Aconitum and Delphinium (Ranunculaceae). DAs have long been a focus of research attention due to their numerous intricate structures and diverse biological activities, especially in the central nervous system (CNS). These alkaloids originate through the amination reaction of tetra or pentacyclic diterpenoids, which are classified into three categories and 46 types based on the number of carbon atoms in the backbone structure and structural differences. The main chemical characteristics of DAs are their heterocyclic systems containing β-aminoethanol, methylamine, or ethylamine functionality. Although the role of tertiary nitrogen in ring A and the polycyclic complex structure are of great importance in drug-receptor affinity, in silico studies have emphasized the role of certain sidechains in C13, C14, and C8. DAs showed antiepileptic effects in preclinical studies mostly through Na+ channels. Aconitine (1) and 3-acetyl aconitine (2) can desensitize Na+ channels after persistent activation. Lappaconitine (3), N-deacetyllapaconitine (4), 6-benzoylheteratisine (5), and 1-benzoylnapelline (6) deactivate these channels. Methyllycaconitine (16), mainly found in Delphinium species, possesses an extreme affinity for the binding sites of α7 nicotinic acetylcholine receptors (nAChR) and contributes to a wide range of neurologic functions and the release of neurotransmitters. Several DAs such as bulleyaconitine A (17), (3), and mesaconitine (8) from Aconitum species have a drastic analgesic effect. Among them, compound 17 has been used in China for decades. Their effect is explained by increasing the release of dynorphin A, activating the inhibitory noradrenergic neurons in the β-adrenergic system, and preventing the transmission of pain messages by inactivating the Na+ channels that have been stressed. Acetylcholinesterase inhibitory, neuroprotective, antidepressant, and anxiolytic activities are other CNS effects that have been investigated for certain DAs. However, despite various CNS effects, recent advances in developing new drugs from DAs were insignificant due to their neurotoxicity

Cyanobacteria—From the Oceans to the Potential Biotechnological and Biomedical Applications

Cyanobacteria are photosynthetic prokaryotic organisms which represent a significantsource of novel, bioactive, secondary metabolites, and they are also considered an abundant source ofbioactive compounds/drugs, such as dolastatin, cryptophycin 1, curacin toyocamycin, phytoalexin,cyanovirin-N and phycocyanin. Some of these compounds have displayed promising results insuccessful Phase I, II, III and IV clinical trials. Additionally, the cyanobacterial compounds applied tomedical research have demonstrated an exciting future with great potential to be developed into newmedicines. Most of these compounds have exhibited strong pharmacological activities, includingneurotoxicity, cytotoxicity and antiviral activity against HCMV, HSV-1, HHV-6 and HIV-1, so thesemetabolites could be promising candidates for COVID-19 treatment. Therefore, the effective large-scale production of natural marine products through synthesis is important for resolving the existingissues associated with chemical isolation, including small yields, and may be necessary to betterinvestigate their biological activities. Herein, we highlight the total synthesized and stereochemicaldeterminations of the cyanobacterial bioactive compounds. Furthermore, this review primarilyfocuses on the biotechnological applications of cyanobacteria, including applications as cosmetics,food supplements, and the nanobiotechnological applications of cyanobacterial bioactive compoundsin potential medicinal applications for various human diseases are discussed.Stockholm UniversityPeer Reviewe

The correlation among residual nitrites, biogenic amines, N‐nitrosamine formation, and degradation occurrence of punicalagin α/β, rosmarinic acid, carnosol, and carnosic acid in extract‐treated sausage during storage

Abstract The aim of this study was to investigate the relation between residual α‐ and β‐punicalagin in Punica granatum L.; PPE and rosmarinic acid, carnosol, and carnosic acid in Salvia eremophila (SE) with residual nitrites, biogenic amines (cadaverine, putrescine, and histamine), N‐nitrosodimethylamine (NDMA), microbial counts, lipid oxidation indices, and color values in extract‐treated sausage over 14 days of storage. Sausage containing SE + nitrite 60 ppm (SSN) showed minimum levels of the residual nitrites (13.14 mg/kg), NDMA (0.74 ± 0.05 μg/kg), and biogenic amine (histamine, 1.8 mg/kg; cadaverine, 3.7 mg/kg; and putrescine, 4.3 mg/kg) due to retarded degradation rate of 285.84–216.44 mg/kg; rosmarinic acid, 41.62–33.16 mg/kg; carnosol, and 88.70–76.73 mg/kg; carnosic acid over storage time. The first‐order kinetic model fitted well for the degradation of rosmarinic acid and carnosol acid in SSN sample. TBA value remained below the threshold limit (0.32 mg kg−1) through 14 days for SSN. Second‐order and zero‐order reaction models had the best agreement with sausages' PV and TBA values, respectively. After 2 weeks of storage, E. coli and Cl. perfringens counts in the SN120 (sausage containing 120 ppm nitrite) and SSN were significantly lower than the other samples (p < .05), with the values 2.1 and 1.5 log cfu/g for SN120 and 2.2 and 1.6 log cfu/g for SSN formulation. Conversely, oxidation indices, residual nitrites, NDMA, and biogenic amine increased in sausage samples containing PPE extracts (SPN) owing to total degradation of α‐ and β‐punicalagin during storage. The results indicated that SE can be used as potential co‐preservative by reducing the levels of required nitrite in food industry

α- Glucosidase Inhibitory and Antioxidant Activities of Moluccella aucheri (Boiss.) Scheen Extracts

Background & Objective: α-Glucosidase is one of the main enzymes in the intestinal absorption of carbohydrates. Inhibition of this enzyme can improve postprandial hyperglycemia in diabetic patients. Also, antioxidants can ameliorate diabetes complications resulted from oxidative stress. In this study α-glucosidase inhibition, antioxidant activity and total phenol content of different extracts and obtained fractions of Moluccella aucheri have been evaluated. Materials & Methods: The ethanol extract of aerial parts of M. aucheri was fractionated using liquid extraction method with petroleum ether, dichloromethane and ethyl acetate, respectively. The extracts and the resulting fractions of M. aucheri were tested against α-glucosidase enzyme from yeast using an in vitro colorimetric model at λ 405 nm. Antioxidant activity was assessed using two different methods, ferric reducing antioxidant power (FRAP) and the scavenging activity of DPPH radicals’ methods. Results: The screening results indicated that the antioxidant activity and total phenolic content of the methanol extract were potentially higher than ethanol extract, while the ethanol extract inhibited α-glucosidase enzyme to a greater extent. Ethyl acetate fraction illustrated potentially the highest antioxidant activity and phenolic content, but its inhibition activity against α-glucosidase was placed after the petroleum ether fraction. Two previously isolated methoxy flavones; genkwanin, 5-hydroxyl-7, 4'-dimethoxyflavone inhibited the α-glucosidase enzyme strongly. Conclusion: Since the ethyl acetate extract has both considerable antioxidant activity and α-glucosidase inhibitory activity, it may be considered as a potential crude drug for diabetes

Silencing Geranylgeranyl Diphosphate Synthase in Nicotiana attenuata Dramatically Impairs Resistance to Tobacco Hornworm1[W][OA]

In bioassays with artificial diets, the 17-hydroxygeranyllinalool diterpenoid glycosides (HGL-DTGs) of Nicotiana attenuata function as antifeedants for the plant's adapted herbivore, tobacco hornworm (Manduca sexta). To determine whether HGL-DTGs have a defensive function in planta, we suppressed HGL-DTG production by silencing the source of the geranylgeranyl diphosphates (GGPPs) required for geranyllinalool biosynthesis, a key intermediate. We used virus-induced gene silencing to suppress transcript levels of GGPP synthase gene (Naggpps) and farnesyl diphosphate (FPP) synthase gene (Nafpps), northern blotting and real-time polymerase chain reaction to quantify transcript accumulations, and radio gas chromatography to analyze prenyltransferase specificity. Silencing Nafpps had no effect on the accumulation of HGL-DTGs but decreased leaf steroid content, demonstrating that DTG-synthesizing enzymes do not use GGPP derived from FPP and confirming FPP's role as a steroid precursor. Unlike plants silenced in the phytoene desaturase gene (Napds), which rapidly bleached, Naggpps-silenced plants had reduced HGL-DTG but not carotenoids or chlorophyll contents, demonstrating that Naggpps supplies substrates for GGPP biosynthesis for HGL-DTGs, but not for phytoene or phytol. Expression of Naggpps in Escherichia coli revealed that the recombinant protein catalyzes the GGPP synthesis from isopentenyl diphosphate and dimethylallyl diphosphate. When fed on silenced plants, hornworm larvae gained up to 3 times more mass than those that fed on empty vector control plants or plants silenced in Nafpps, the trypsin protease inhibitor gene, or the putrescine N-methyltransferase gene. We conclude that HGL-DTGs or other minor undetected diterpenoids derived from GGPP function as direct defenses for N. attenuata and are more potent than nicotine or trypsin protease inhibitors against attack by hornworm larvae

Bioassay guided purification of cytotoxic natural products from a red alga Dichotomaria obtusata

Different solvent extracts of Dichotomaria obtusata (J. Ellis & Solander) Lamark, Galaxauraceae, a red algae collected from the coast of Bushehr in the Persain Gulf, was investigated for its cytotoxic properties and chemical constituents. The fresh alga, after extraction with methanol and dichloromethane were combined and partitioned between water, dichloromethane and ethyl acetate. The above fractions were then tested against MOLT-4 (human lymphoblastic leukemia) cancer cell line. The IC50 values of the dichloromethane and ethyl acetate layers of the crude extract were 29.8 ± 3.1 and 30.6 ± 7.9 μg/ml against MOLT-4 cells, respectively, while the water layer showed a week activity with IC50 > 50 μg/ml. After fractionation of the active extracts using open column chromatography over silica gel and preparative thin layer chromatography purification, two terpenoid derived compounds, trans-phytol palmitate and γ-tocopherol were isolated from the dichloromethane and ethyl acetate extracts. The structures of the compounds were elucidated using different spectral data including 1H NMR, 13C NMR, HSQC, HMBC and EI-MS. The IC50 values of compounds trans-phytol palmitate, γ-tocopherol and an undetermined mixture of compounds (F-13-14) were determined as 43.4 ± 1.6, – and 20.3 ± 6.2 μg/ml against LS180 (human colon adenocarcinoma); 53.2 ± 9.3, >100 and 27.6 ± 6.9 μg/ml against MCF-7 (human breast adenocarcinoma) and 40.0 ± 4.1, 48.8 ± 1.8 and 15.9 ± 0.3 μg/ml against MOLT-4 cell lines, respectively, which were comparable to the IC50 values of standard anticancer agent, cisplatin against the same cell lines. The red algae collected from the Persian Gulf contained substances that could inhibit the growth of human cancer cell lines and may represent a natural source for the discovery of novel anticancer agents. Keywords: Dichotomaria obtusata, Red algae, Trans-phytol palmitate, Tocopherol, Cytotoxic activit

Antifungal effect of the bark and root extracts of Punica granatum on oral Candida isolates

Background and Purpose: Oral candidiasis is one of the most common fungal infections in humans. The treatment and prophylaxis of the patients suffering from this infection require the identification of new anti-Candida agents with no side effects or toxicity like medicinal plants. The present study was conducted to compare the antifungal activities of the aqueous, ethanolic, and methanolic extracts of the bark and roots of P. granatum with those of two routine antifungal agents (i.e., fluconazole and nystatin) on oral Candida strains isolated from liver transplant recipients. Materials and Methods: Minimum inhibitory concentrations (MICs) of the ethanolic, methanolic, and aqueous extracts of the bark and root of Punica granatum against C. albicans and C. glabrata isolated from oral cavities were evaluated according to the CLSI M27-A3. All data were analyzed in SPSS (version 16.0) by pairwise comparison and Kruskal-Wallis test. Results: The MIC50 and MIC90 values for the methanolic and ethanolic extracts of the bark and root of P. granatum against C. albicans were both obtained as 0.05 mg/ml with the geometric mean (GM) of 0.07. Furthermore, the MIC90 values for the aqueous extracts of bark and root were estimated as 0.05 and 0.2 mg/ml, respectively. With regard to C. glabrata, the MIC50 and MIC90 values for the methanolic and ethanolic extracts of the bark and root were 0.05 mg/ml. However, the MIC90 value for the aqueous extract against this species was obtained as 25 mg/ml. The GM values for the aqueous extracts of the bark and root were 9.49 and 0.32, respectively. Conclusion: As the findings indicated, the methanolic and ethanolic extracts of the bark and root of Punica granatum had anti-Candida activities. Therefore, they can be considered as mouthwash or toothpaste to prevent and treat Candida infections in the oral cavity