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The inhibition potential of α-glucosidase enzyme by crude- dichloromethane, methanol, and ethanol -extracts of Rydingia persica were evaluated using colorimetric method. We have isolated four labdane diterpenoids: 15, 16- epoxy-3α, 7β, 9α -trihydroxylabdan-13- (16), 14-dien-6-one ( 1 ), 15, 16- epoxy-3α, 7α, 9α -trihydroxylabdan-13- (16), 14-dien-6-one ( 2 ), 9, 13, 15, 16-diepoxy- 3α, 7β, 15α (β)- trihydroxy-labdan- 6 one ( 3 , 4 ) from the most potent enzyme inhibitor fraction; the ethyl acetate soluble part of ethanol extract of the aerial parts of R. persica . The structures of the compounds were elucidated by their 1 H and 13 C NMR and ESIMS spectral data analyses. The enzyme inhibition potential of the compounds was evaluated against acetylcholine esterase (AChE) and α-glucosidase by simulation studies. The predicted binding energy of most diterpenes towards mouse AChE enzyme was low, while the binding energy of diterpenes towards α-glucosidase enzyme was moderate to potent.

Introduction: Isolation and characterization of bioactive components from complex matrices of marine or terrestrial biological origins are the most challenging issues for natural product chemists. Biochemometric is a new potential scope in natural product analytical science, and it is a methodology to find the compound's correlation to their bioactivity with the help of hyphenated chromatographic techniques and chemometric tools., Objectives: The present review aims to evaluate the application of chemometric tools coupled to chromatographic techniques for drug discovery from natural resources., Methods: The searching keywords "biochemometric," "chemometric," "chromatography," "natural products bioassay," and "bioassay" were selected to search the published articles between 2010-2023 using different search engines including "Pubmed", "Web of Science," "ScienceDirect," and "Google scholar.", Results: An initial stage in natural product analysis is applying the chromatographic hyphenated techniques in conjunction with biochemometric approaches. Among the applied chromatographic techniques, liquid chromatography (LC) techniques, have taken up more than half (53%) and also, mass spectroscopy (MS)-based chromatographic techniques such as LC-MS are the most widely used techniques applied in combination with chemometric methods for natural products bioassay. Considering the complexity of dataset achieved from chromatographic hyphenated techniques, chemometric tools have been increasingly employed for phytochemical studies in the context of determining botanicals geographical origin, quality control, and detection of bioactive compounds., Conclusion: Biochemometric application is expected to be further improved with advancing in data acquisition methods, new efficient preprocessing, model validation and variable selection methods which would guarantee that the applied model to have good prediction ability in compound relation to its bioactivity., (© 2024 John Wiley & Sons Ltd.)

Cytotoxicity-guided purification of Juniperus polycarpos K. Koch leaves (Cupressaceae) led to the isolation of a new labdane diterpenoid, 3-(acetyloxy)-acetylisocupressic acid ( 1 ), together with isocupressic acid ( 2 ), 3,4-dimethoxycinnamoyl alcohol ( 3 ) and deoxypodophyllotoxin ( 4 ). The chemical structures of 1-4 were established by detailed 1D and 2D NMR, HRFAB-MS and LRESI-MS, as well as by comparing the spectral data with those reported in the literature. Compound 1 was ineffective against HepG2 cells and protease enzyme, while 2 showed potent cytotoxicity against HepG2 cells (IC 50 of 3.73 μg/mL) compared to cisplatin (IC 50 of 12.65 μg/mL). Computational analyses with CDK1 protein (a prominent protein in the cell cycle of HepG2 cells) revealed the binding affinity of 2 (-31.86 kcal/mol) was better than 1 (-19.70 kcal/mol) because the acetoxy groups did not allow binding deeply to the ATP binding site. Compounds 2 and 4 moderately inhibited the protease activity (IC 50 = 52.7 and 63.0 μg/mL, respectively). Further in vitro and in vivo studies on the plant are strongly recommended.

Objectives: Type 2 diabetes is a common metabolic disease affecting millions of people worldwide. α-Glucosidase inhibitors can be used as one of the therapeutic approaches to decrease the postprandial glucose levels through the inhibition of carbohydrate hydrolysis. Medicinal plants are one of the main sources of α-glucosidase's natural inhibitors. In this study, we report the inhibitory effects of 50 different accessions of 32 Salvia species against α-glucosidase., Methods: To estimate the relative potency of the crude extracts, the inhibitory activities of the 80% methanol of the plants extracts were determined in three different concentrations (1000, 500 and 250 µg/ml) and compared to that of acarbose as the positive control., Results: S. multicaulis, S. santolinifolia, S. dracocephaloides, and S. eremophila were stronger inhibitors than acarbose (p < 0.05) with IC 50 values in the range of 26.23- 92.35 µg/mL. According to the LC-PDA-ESIMS and NMR analysis of crude extracts of the studied Salvia species, 8 phytochemicals including luteolin-7- O -glucoside ( 1) luteolin-7- O -glucuronide ( 2 ), apigenin-7- O -glucoside ( 3 ), apigenin-7- O -glucuronide ( 4 ), Hispidulin-7- O -glucuronide ( 5 ), hispidulin-7- O -glucoside ( 6 ), rosmarinic acid ( 7 ), carnosol ( 8 ) and carnosic acid ( 9 ) were identified as the most common α -glucosidase inhibitors. The above compounds constituted the major compounds in the active Salvia species in the range of 1.5-95.0%. Among them rosmarinic acid (39-95%) was detected in almost all potent α -glucosidase inhibitor species. Therefore, it can be considered as a biochemical marker in the antidiabetic Salvia species in addition to the other minor compounds., Conclusions: Considering the high α-glucosidase inhibitory potential of the four- out of fifty Salvia species, they are suggested for further in vivo antidiabetic tests as potential medicinal plants., Competing Interests: Conflict of InterestThe authors declared that they have no conflict of interest. The financial support of the present research was provided by the research council of Shiraz University of Medical Sciences, Shiraz, Iran (grant no. 17131). Amir Reza Jassbi is the mentor and founder of a startup company “Aryana Phytochemistry of Tirazis”., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

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., Competing Interests: The authors declare that they have no conflict of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

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.

Background: In recent decades, algae have attracted worldwide attention for their great biological activities, such as antidiabetic and antibacterial properties., Objectives: We measured antibacterial and α-glucosidase inhibition potential of methanol and 80% methanol extracts of three brown algae species, Polycladia myrica , Padina antillarum , and Sargassum boveanum , and a red alga, Palisada perforata , from the Persian Gulf coasts., Methods: Antibacterial activity of the algal extracts was assessed by broth dilution method against three gram-negative and -positive bacteria, including Escherichia coli , Klebsiella pneumonia , Pseudomonas aeruginosa ; Staphylococcus epidermidis , Staphylococcus aureus , and Bacillus subtilis , respectively. Furthermore, the yeast's α-glucosidase inhibition of the algal extracts was measured via colorimetric assay. In addition, we investigated the beneficial effect of 80% MeOH extract of S. boveanum on the blood glucose levels in streptozotocin-induced diabetic rats., Results: The MeOH extract of S. boveanum was the best antibacterial extract with MIC = 2.5 mg/mL against all bacterial strains except for E. coli . The MeOH and 80% MeOH extracts of P. myrica and P. antillarum inhibited α-glucosidase at most with IC 50 values of 12.70 ± 1.88 µg/mL and 13.06 ± 4.44 µg/mL, respectively. The oral gavage of S. boveanum extract in streptozotocin- (STZ-) induced diabetic rats resulted in decreasing their postprandial blood glucose levels. The algae and acarbose decreased blood glucose levels after sucrose administration in 60 minutes, compared to the non-drug-treated animals, with p values of 0.03 and 0.007, respectively., Conclusions: Overall, due to the in vitro and in vivo antidiabetic potential of S. boveanum , we suggest the alga as a new source for the isolation and identification of potential antidiabetic and antibacterial compounds., Competing Interests: The project is supported by the Shiraz University of medical sciences. ARJ is a reviewer of IJPR. No one of us has been paid by a private company for the present research., (Copyright © 2023, Moheimanian et al.)

Salvia grossheimii is a perennial herb with antidiabetic and cytotoxic constituents. In continuation of our study on S. grosshiemii to identify the bioactive phytochemicals, we have reported the characterization of seven undescribed triterpenoids. The aerial parts of the plant were extracted in dichloromethane and its constituents were isolated using chromatography techniques. The structures of compounds were identified using 1D, 2D NMR, and ESI-MS spectral data. Seven new oleanane- and ursane-type triterpenoids ( 1 - 7 ) were identified in S. grossheimii . The structures of 1 - 7 were characterized as; 2 α -hydroxy-3 β -acetoxy-olean-9(11),12-diene ( 1 ), 2 α -acetoxy-3 β -hydroxy-olean-9(11),12-diene ( 2 ), 3 β -acetoxy-olean-18-ene,2 α ,11 α -diol ( 3 ), 2 α -hydroxy-3 β -acetoxy-urs-9(11),12-diene ( 4 ), 2 α -acetoxy-3 β -hydroxy-urs-9(11),12-diene ( 5 ), 2 α ,3 β -diacetoxy-urs-12-ene-11 α ,20 β -diol ( 6 ), 2 α ,3 β -diacetoxy-urs-9(11),12-diene-20 β -ol ( 7 ). Triterpenoids ( 2 , 5 , and 7 ) were intramolecular transesterification or dehydration products of their corresponding isomers or allylic alcohol in the C rings, respectively, produced in-situ during NMR spectroscopy. Virtual screening of 1 - 7 was performed with molecular docking analysis to identify the potential SARS-CoV-2 and α -glucosidase inhibitors using the smina molecular docking algorithm. The best binding energy values (kcal/mol) against COVID-19 main protease M pro were calculated for 6 (-8.77) and 7 (-8.68), and the higher binding affinities toward human α -glucosidase were obtained for 2 (-9.39) and 6 (-8.63). This study suggests S. grossheimii as a rich source of bioactive triterpenoids and introduces new natural compounds. Considering the high binding energy values of 2 , 6 , and 7 , these structures could be candidates for anti-COVID-19 and antidiabetic drug development in the future.

Background: Salvia extracts have various biological activities and are rich sources of bioactive metabolites., Objectives: We identified five phytochemicals from S. compressa extract and assessed its biological properties., Methods: The plant's shoots were extracted using dichloromethane, and the constituents were isolated using column chromatography. High-resolution NMR spectroscopy characterized the chemical structures of the compounds (1 - 5). The cytotoxic effect of the extract was examined against MCF-7 cells by MTT reduction assay, while cisplatin was tested as a reference cytotoxic compound. The antibacterial activity was assessed using nutrient broth micro-dilution (NBMD), and chloramphenicol was used as the positive control., Results: Citrostadienol (1), β-sitosterol (2), two glyceride esters of linolenic, linoleic, and palmitic acids (3, 4), and geraniol (5) were isolated from S. compressa for the first time. The extract showed activity against MCF-7 breast cancer cells and reduced cell viability to 68.2 ± 13.1% compared to the control drug at the concentration of 50 µg/mL, while it was not active against seven test bacteria., Conclusions: The anti-complementary activity of the isolated steroids suggests S. compressa for future anti-inflammatory research., Competing Interests: Conflict of Interests: ARJ is reviewer of IJPR. The paper was supported by a NIMAD Grant. There is no support from any company in which the authors have stock shares. No patents and no consultant fees are earned regarding this manuscript. Omidreza Firuzi is not an editorial member of IJPR but may be a reviewer of some papers in IJPR., (Copyright © 2022, Author(s).)

Background: Brown algae have gained worldwide attention due to their significant biological activities, such as antidiabetic properties. In the present study, the antidiabetic properties of six brown algae from the Persian Gulf were investigated., Methods: An experimental study was conducted from 2017 to 2019 to examine the inhibitory effects of six brown algae against the α-glucosidase activity. Methanol (MeOH) and 80% MeOH extracts of Colpomenia sinuosa , Sargassum acinaciforme , Iyengaria stellata , Sirophysalis trinodis , and two accessions of Polycladia myrica were analyzed. The effect of 80% MeOH extracts of Sirophysalis trinodis on blood glucose levels in streptozotocin-induced diabetic rats was evaluated. Chemical constituents of brown algae were analyzed using thin-layer chromatography and liquid chromatography-mass spectrometry techniques. Data were analyzed using SPSS software, and P<0.05 was considered statistically significant., Results: The 80% MeOH extracts of Iyengaria stellata (IC 50 =0.33±0.15 μg/mL) and Colpomenia sinuosa (IC 50 =3.50±0.75 μg/mL) as well as the MeOH extracts of Colpomenia sinuosa (IC 50 =3.31±0.44 μg/mL) exhibited stronger inhibitory effect on α-glucosidase than the acarbose (IC 50 =160.15±27.52 μg/mL, P<0.001). The 80% MeOH extracts of Sirophysalis trinodis reduced postprandial blood glucose levels in diabetic rats compared to the control group (P=0.037). Fucoxanthin was characterized as the major antidiabetic agent in most of the algal extracts., Conclusion: Sirophysalis trinodis is recommended as a novel source for isolation and identification of potential antidiabetic compounds due to its high in vivo and in vitro antidiabetic effects., Competing Interests: None declared., (Copyright: © Iranian Journal of Medical Sciences.)

The roots of Salvia spinosa L. (Lamiaceae) were extracted with hexane, dichloromethane (DCM) and ethyl acetate. The DCM extract exhibited cytotoxic activity (IC 50 32.7 µg/mL) against MFC-7 breast cancer cell line in MTT colorimetric bioassay. Ferruginol ( 1 ), taxodione ( 2 ), 12-deoxy-6-hydroxy-6,7-dehydroroyleanone ( 3 ), 14-deoxycoleon U ( 4 ), 15-deoxyfuerstione ( 5 ) and taxodone ( 6 ) were isolated from the DCM roots extract. Their structures were elucidated by a combination of spectroscopic analyses including EIMS and 1 H- and 13 C NMR spectra. The cytotoxicity of compound 3 was determined against MCF-7 and K562 cell lines and compared with the other compounds. A pharmacophore model was built based on potent input compounds to resolve important pharmacophore features responsible for cytotoxic activity of the isolated compounds.

Context: Ircinia mutans Wilson (Irciniidae) is a sponge with antimicrobial and cytotoxic constituents., Objective: Our objective was to characterise the cytotoxic constituents of two seasonal collections of I. mutans ., Materials and Methods: The sponges were extracted in methanol-dichloromethane and their constituents were purified and characterised using column chromatography, GC-MS, 1 D and 2 D NMR. Anti-proliferative activities of the compounds, were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay (0.25-100 μg/mL, 72 h) against leukaemia (MOLT-4), breast (MCF-7) and colon cancer (HT-29) human cells., Results: Three furanosesquiterpoids; furodysin ( 1 ), ent -furodysinin ( 2 ) and furoircin ( 3 ) and ten sterols were characterised in I. mutans , for the first time. Cholesterol ( 4 ), cholesta-5, 7-dien-3β-ol ( 5 ) and ergosterol ( 6 ) were determined in the sponge from the winter collections, while cholesta-5, 22-dien-3β-ol ( 7 ), 24-methyldesmosterol ( 8 ), campesterol ( 9 ), stigmasterol ( 10 ), γ-ergostenol ( 11 ), chondrillasterol ( 12 ) and γ-sitosterol ( 13 ) were detected in the summer samples. The steroids from the winter collection exhibited cytotoxic activity with IC 50 values of 13.0 ± 0.9, 11.1 ± 1.7 and 1.1 ± 0.4 µg/mL, against the mentioned cancer cell lines, respectively, while those from the summer sample, showed greater activity, IC 50 = 1.1 ± 0.2 μg/mL against MOLT-4. The purified steroids showed potent MOLT-4 cytotoxic activity, IC 50 values = 2.3-7.8 µg/mL., Discussion and Conclusion: The present study suggests that I. mutans is a rich source of cytotoxic steroids, and introduces 3 as new natural product. Considering the high cytotoxic activity of the steroids, these structures could be candidates for anticancer drug development in future research.

Introduction: Rosa damascena Mill distillate and its essential oil are widely used in cosmetics, perfumes and food industries. Therefore, the methods of detection for its authentication is an important issue., Objectives: We suggest colorimetric sensor array and chemometric methods to discriminate natural Rosa distillate from synthetic adulterates., Material and Methods: The colour responses of 20 indicators spotted on polyvinylidene fluoride (PVDF) substrate were monitored with a flatbed scanner; then their digital representation was analysed with principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and soft independent modelling of class analogy (SIMCA)., Results: Accurate discrimination of the diluted- and synthetic-mixture samples from the original ones was achieved by PLS-DA and SIMCA models with error rate of 0.01 and 0, specificity of 0.98 and 1, sensitivity of 1 and 1, and accuracy of 0.98 and 0.96, respectively. Discrimination of the synthetic adulterate from the original samples was achieved with error rate of 0.03 and 0.03, specificity of 0.94 and 0.93, sensitivity of 1 and 1, and accuracy of 0.93 and 0.71 with PLS-DA and SIMCA models, respectively. Moreover, the chemical constituents of the samples were analysed using dispersive liquid-liquid microextraction and gas chromatography-mass spectrometry (GC-MS). The main constituents of the distillate were geraniol, citronellol, and phenylethyl alcohol in different percentages, in both original and synthetic adulterate samples., Conclusion: These results point out the successful combination of colorimetric sensor array and PLS-DA and SIMCA as a fast, sensitive and inexpensive screening tool for discrimination of original samples of R. damascena Mill distillate from those prepared from synthetic Rosa essential oils., (© 2021 John Wiley & Sons, Ltd.)

Bioassay-guided fractionation of a dichloromethane extract of the aerial parts of Salvia urmiensis, an endemic plant species of Iran, led to the isolation of two new cytotoxic ursane triterpenoids, Salvurmin A and Salvurmin B. Their structures were elucidated by a combination of 1D and 2D NMR, HR-ESI-MS, IR and UV analysis. Cytotoxicity of the above-mentioned compounds were evaluated against two human cancerous cell lines (SW1116, MCF-7). IC 50 values for Salvurmin A and Salvurmin B on colon cancer cell line (SW1116) were 41.6 ± 2.6 and 23.2 ± 0.4 μM respectively, in comparison to cisplatin as control positive. In addition, these two compounds exhibited cytotoxic activity on breast cancer cell line (MCF-7) with an IC 50 of 54.2 ± 5.3 and 40.2 ± 3.1 μM for Salvurmin A and Salvurmin B, respectively. The cytotoxic activities of these two compounds present a promising potential for the future investigation on this endemic species of Salvia., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Cyanobacteria are photosynthetic prokaryotic organisms which represent a significant source of novel, bioactive, secondary metabolites, and they are also considered an abundant source of bioactive compounds/drugs, such as dolastatin, cryptophycin 1, curacin toyocamycin, phytoalexin, cyanovirin-N and phycocyanin. Some of these compounds have displayed promising results in successful Phase I, II, III and IV clinical trials. Additionally, the cyanobacterial compounds applied to medical research have demonstrated an exciting future with great potential to be developed into new medicines. Most of these compounds have exhibited strong pharmacological activities, including neurotoxicity, cytotoxicity and antiviral activity against HCMV, HSV-1, HHV-6 and HIV-1, so these metabolites 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 existing issues associated with chemical isolation, including small yields, and may be necessary to better investigate their biological activities. Herein, we highlight the total synthesized and stereochemical determinations of the cyanobacterial bioactive compounds. Furthermore, this review primarily focuses on the biotechnological applications of cyanobacteria, including applications as cosmetics, food supplements, and the nanobiotechnological applications of cyanobacterial bioactive compounds in potential medicinal applications for various human diseases are discussed.

Three undescribed dammarane-type saponins, russelliinosides A-C, together with a common sterol (β-sitosterol), an abietane diterpenoid (18-hydroxyferruginol), two oleane triterpenoids (daturaolone and oleanolic acid), an ursane triterpenoid (ursolic acid) as well as three 5-hydroxyflavones (cirsimaritin, eupatorin, and salvigenin) were isolated from a dichloromethane extract of the aerial parts of Salvia russellii Benth. The chemical structures of the aforementioned compounds were characterized, using detailed spectroscopic analyses, including high-resolution mass spectrometry and 1D and 2D NMR ( 1 H- 1 H COSY, TOCSY, HSQC, HMBC and NOESY) spectroscopy as well as physicochemical properties. Cytotoxic effects of S. russellii extract and the three isolated russelliinosides were tested against MCF-7 human breast and A549 lung cancer, as well as non-cancer NIH/3T3 cells using MTT reduction assay. Russelliinosides A and B exhibited cytotoxic activities with IC 50 values of 7.1 and 30.7 μg/ml against MCF-7 and 33.9 and 69.4 μg/ml against A549 cells, respectively, while russelliinoside C did not show cytotoxicity against cancer cells. On the other hand, russelliinoside A showed an IC 50 value of 31.5 μg/ml against NIH/3T3 cells, while russelliinosides B and C had no effect on the viability of these non-cancer cells., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Iran is one of the main hubs for sage's diversity in Asia. Generally, prediction and characterization of the chemical structures of the specialized metabolites that have significant role in the bioactivity of a plant remains a significant challenge. In this study, 50 different accessions of 32 Salvia species in 2015 and 2017 were collected and extracted for their phenolics, using 80 % methanol. LC-PDA-ESIMS analyses was coupled with multivariate analysis to identify the specific metabolites in the plant extracts, responsible for the antioxidant activity. Based on the variable importance in projection (VIP) method on the Genetic algorithm combined with PLS (GA-PLS) models, eighteen peaks were detected as multifunctional compounds. The putative phenolic compounds were attributed to apigenin-O-diglucoside, rutin, cynaroside, luteolin-7-O-glucoronide, apigenin-7-O-glucoside, apigenin-7-O-glucuronide, hispidulin-7-O-glucuronide, hispidulin-7-O-glucoside, rosmarinic acid, salvianolic acid B derivative, cirsimaritin, eupatorin, and carnosol. This investigation showed that the Salvia's extract can facilitate an opportunity for rapid detection, isolation and development of antioxidant agents., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The marine environment with its vast biological diversity encompasses many organisms that produce bioactive natural products. Marine microorganisms are rich sources of compounds from many structural classes with a multitude of biological activities. The biosynthesis of microbial natural products depends on a variety of biotic and abiotic factors in the marine environment, including temperature, nutrients, salinity and interaction with other microorganisms. Terpenoids, as one of the most important groups of natural products in terrestrial microorganisms are important metabolites for marine microorganisms. Here, we have reviewed the chemistry, biosynthesis and pharmacological activities of terpenoids, extracted from marine microbes, and then survey their potential applications in drug development. We also discussed the different habitats in which marine microorganisms are found including sediments, the flora, such as seaweeds, sea grasses, and mangroves as well as the fauna like sponges and corals. Amongst these habitats, marine sediments are the major source for terpenoids producing microorganisms. The marine bacteria produce mostly meroterpenoids, while the fungi are well known for production of isoprenoids. Interestingly, marine-derived microbial terpenoids have some structural characteristics such as halogenation, which are catalyzed by specific enzymes with distinct substrate specificity. These compounds have anticancer, antibacterial, antifungal, antimalarial and anti-inflammatory properties. The information collected here might provide useful clues for developing new medications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Two polyhydroxylated oleanane and seven ursane triterpenoids were isolated from aerial parts of Salvia grossheimii. The chemical structures of the undescribed triterpenoids (1-6) were characterized using 1 and 2 D NMR and ESI-MS spectral data as; 2α, 3β, 11α -trihydroxy-olean-12- ene (1), 2α, 3β, 11α-trihydroxy-olean-18-ene (2), 2α- acetoxy-urs-12-ene-3β, 11α, 20β-triol (3), 3-keto-urs-12-ene-1β, 11α, 20β -triol (4), 2α, 3β-diacetoxy-urs-12-ene-1β, 11α, 20β -triol (5), and 3β-acetoxy-urs-12-ene-1β, 11α, 20β -triol (6). All compounds were evaluated for the in vitro α-glucosidase inhibitory and cytotoxic activities against MCF-7 human cancer cell line. Compounds 1, 2, 4, and 6 showed in vitro α-glucosidase inhibitory activity with IC 50  = 43.6-198.4 µM, which were more potent than the antidiabetic medicine, acarbose. The remaining compounds; 3, and 7-9 showed potent cytotoxic activity (IC 50  = 6.2-31.9 µM) against the cancerous cell line, while the potent α-glucosidase inhibitors were inactive. Molecular docking analysis and kinetic studies were applied to investigate the structure activity relationships and mechanisms of the human and Saccharomyces cerevisiae α-glucosidase inhibitory of the purified compounds. Comparing the high cytotoxicity and α-glucosidase inhibitory of the oleanane and ursane type triterpenoids suggest them as potential lead compounds for further research in anticancer and antidiabetic research., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Further investigations on phytochemical constituents of dichloromethane extract from roots of Salvia lachnocalyx ( S. lachnocalyx) led to the isolation and identification of eight known diterpenoids from this plant for the first time. The chemical structures of the purified compounds were elucidated using spectroscopic analyses including EI-MS, 1 H and 13 C NMR and by comparison of the resulting spectra with those reported in the literature. Then, the cytotoxic activity of identified compounds was examined against two human cancer cell lines MCF-7 (human breast adenocarcinoma) and K562 (human chronic myelogenous leukemia). Molecular docking of promising cytotoxic compounds were performed by AutoDock Tools 1.5.4 program in the active site of Topoisomerase I. Eight known diterpenoids; 12-hydroxysapriparaquinone ( 1 ), 15-deoxyfuerstione ( 2 ), horminon ( 3 ), 7α-acetoxyroyleanone ( 4 ), 11β-hydroxymanoyl oxide ( 5 ), microstegiol ( 6 ), 1-keto-aethiopinone ( 7 ) and 14-deoxycoleon U ( 8 ) were isolated of dichloromethane extract from roots of salvia lachnocalyx . Compounds 2 , 3 , 6, and 8 showed cytotoxic activity against MCF-7 (human breast adenocarcinoma) and K562 (human chronic myelogenous leukemia) cell lines with IC 50 values in the range of 2.63-11.83 µg/mL. The inhibition of" topoisomerase I" was suggested by molecular docking calculations as the mechanism of cytotoxicity of the tested compounds. According to cytotoxic assay and docking results, it is suggested that compounds 2 , 3 , 6 , and 8 have good potential as anticancer agents.

Among specialized metabolites, terpenoids are well-known for their cytotoxic activity. Several of them have been isolated from sage plants and assayed for their potential therapeutic use against cancer. In this study, we report the effects of three potent anticancer terpenoids previously isolated from Salvia lachnocalyx , including geranyl farnesol ( 1 ), sahandinone ( 2 ), and 4-dehydrosalvilimbinol ( 3 ) on cancer cell cycle alterations and reactive oxygen species (ROS) production. Interactions of compounds 1-3 with topoisomerase I were also investigated by using molecular docking and dynamics simulation. Accumulation of cells in sub-G1 phase of the cell cycle indicated that all tested compounds induce apoptosis in MOLT-4 cancer cells. Measurement of ROS production demonstrated that this mechanism is not involved in the induction of apoptosis. We suggest topoisomerase I inhibition as the mechanism of cytotoxic activity of compounds 1-3 based on docking and molecular dynamics (MD) calculations. These natural terpenoids could be considered as good candidates for further development as anticancer agents.

We isolated an actinobacterium, Streptomyces sp. strain SP 85 from the marine sponge Dysidea avara. Polyphasic identification of the microorganism showed that the strain SP 85 had high 16S rRNA gene similarity (99%) with Streptomyces olivaceus strain NBRC 12805, while some physiological and biochemical differences were observed. A cytotoxic compound, SP 85 was isolated from the active culture extract of the strain SP 85 by bioassay-guided purification over silica gel column chromatography, preparative TLC, and HPLC. The structure elucidation based on the spectroscopic analysis, including UV, ESI-MS, and 13 C NMR data revealed that SP 85 compound is an analog of anti-tumor drug, "olivomycin A". The SP 85 compound showed high cytotoxic activity against three human cancer cell lines, including SW480, HepG2, and MCF7 with IC 50 values of 16, 93, and 78 nM, respectively. SP 85 exhibited significantly (2-10 times) higher cytotoxicity against the tumor cell lines in comparison with HUVECs as the normal cell line, which also induced apoptosis in the tested cancerous cell line. This is the first report on the production of an "olivomycin A" derivative by a sponge-associated Streptomyces , showing the great potential of sponge-associated actinobacteria in producing cytotoxic natural products., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© King Abdulaziz City for Science and Technology 2019.)

Purpose: Marine sponges are rich sources of anticancer metabolites. Axinella sinoxea is a less studied sponge, found in the Larak Island's waters, of the Persian Gulf. In the present study, we have explored the cytotoxic properties and chemical constituents of A. sinoxea., Methods: Repeated silica gel flash column chromatography of methanol extract of the Axinella sinoxea sponge, yielded fatty acid and sterol fractions. These fractions were analyzed by GC-MS and their anti-proliferative activities were evaluated by MTT assay against three human cancer cell lines including MOLT-4, MCF-7 and HT-29 as well as NIH/3 T3 fibroblast cells. The sterol-rich fractions were pooled and purified by HPLC and its sub fractions' cytotoxic activities were evaluated by MTT assay against MOLT-4 and NIH/3 T3 cells., Results: The GC-MS spectral analysis of a fraction eluted with hexane: diethyl ether (90: 10), resulted in the identification of twelve fatty acids, including five linear chain saturated fatty acids; tetrdecanoic acid (1), pentadecanoic acid (3), hexadecanoic acid (5), heptadecanoic acid (7), and octadecanoic acid (10); one branched chain isoprenoid fatty acid, 4,8,12-trimethyltridecanoic acid (2); four monoenoic fatty acids; 9-hexadecenoic acid (4), 7-methyl-6-hexadecanoic acid (6), 9-octadecenoic acid (8) and 11-octadecenoic acid (9) and two polyunsaturated fatty acids; 5,8,11,14-eicosatetraenoic acid (11) and 4,7,10,13,16,19-docosahexaenoic acid (12). Spectral analysis of a non-polar fraction eluted with hexane: diethyl ether (85: 15), resulted in the identification of eight steroids including: cholesta-5,22-dien-3β-ol (13), cholest-5-en-3β-ol (14), ergosta-5,22-dien-3β-ol (15), ergost-5-en-3β-ol (16), stigmasta-5,22-dien-3β-ol (17), γ-sitosterol (18), 33-norgorgosta-5,24(28)-dien-3β-ol (19) and stigmasta-5,24(28)-dien-3β-ol (20). Fatty acids-containing fraction was active against HT-29 cell line with IC 50 26.52 ± 8.19 μg/mL, while the steroids-rich fraction was active against the three above mentioned cell lines with IC 50 values of 1.20 ± 0.24, 4.12 ± 0.40 and 2.47 ± 0.31 μg/mL, respectively. All of the above-mentioned fractions and sub-fractions were inactive (IC 50 s > 50 μg/mL) when assayed against normal fibroblast cells., Conclusion: The present study suggests A. sinoxea as a potential natural source of cancer chemotherapeutics. Graphical abstract Cytotxic constituents of Axinella sinoxea.

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.

Species of Nicotiana grow naturally in different parts of the world and have long been used both medicinally and recreationally by human societies. More recently in our history, Nicotiana tabacum has attracted interest as one of the most economically important industrial crops. Nicotiana species are frequently investigated for their bioactive natural products, and the ecological role of their specialized metabolites in responses to abiotic stress or biotic stress factors like pathogens and herbivores. The interest of tobacco companies in genetic information as well as the success of a few wild tobacco species as experimental model organisms have resulted in growing knowledge about the molecular biology and ecology of these plants and functional studies of the plant's natural products. Although a large number of reviews and books on biologically active natural products already exists, mostly from N. tabacum, we focus our attention on the ecological roles and biological activity of natural products, versus products from cured and processed material, in this Review. The studied compounds include alkaloids, aromatic compounds, flavonoids, volatiles, sesquiterpenoids, diterpenes alcohols, and sugar esters from trichomes of the plants, and recently characterized acyclic hydroxygeranyllinalool diterpene glycosides (HGL-DTGs). In this Review (1800s-2017), we describe the above-mentioned classes of natural products, emphasizing their biological activities and functions as they have been determined either in bioassay-guided purification approaches or in bioassays with plants in which the expression of specific biosynthetic genes has been genetically manipulated. Additionally, a review on the history, taxonomy, ecology, and medicinal application of different Nicotiana species growing around the globe presented in this Review may be of interest for pharmacognosists, natural products, and ecological chemists.

Sahandinone (1), 12-deoxysalvipisone (2), miltirone (3), 7α-acetoxyroyleanone (4), and labda-7,14-dien-13-ol (5) were isolated from the roots of Salvia rhytidea Benth. (Lamiaceae). Their structures were elucidated by a combination of spectroscopic analyses including EIMS and NMR. The 13 C NMR spectroscopic data were revised for the quaternary carbons of both 1 and 3 with the help of HMBC spectra in respect to the spectral data previously reported in the literature. Compounds 1 and 3, two very potent anticancer agents, were isolated in high yields from the roots of the plant. The biological activities of the plants' constituents were reported in the literature as antimicrobial, cytotoxic and antimalarial are discussed in this article.

Context The genus Anthemis L. (Asteraceae) comprises about 195 species which are widely used in the pharmaceutical, cosmetic and food industries. Objective Anthemis mirheydari Iranshar, an endemic plant from Iran, was investigated for its cytotoxic properties and chemical constituents. Materials and methods The whole parts of the plant (320 g) were extracted by dichloromethane and methanol for four days, successively. The cytotoxic activity of both dichloromethane and methanol extracts were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric methods against three human cancer cell lines including LS180, MCF-7 and MOLT-4. Different concentrations (10-100 μg/mL) of the plant extracts were tested to obtain IC50 values. The dichloromethane extract of A. mirheydari was subjected to silica gel-column and thin layer chromatography for purification of its chemical constituents and the isolated compounds were further tested against MOLT-4 cells. The structures of the pure compounds were elucidated using different spectral data including nuclear magnetic resonance and electron impact mass spectra. Results The IC50 values of the dichloromethane extract were 30.8 ± 6.7, 25.2 ± 6.5 and 8.6 ± 1.1 μg/mL (means ± standard error) for the above-mentioned cell lines, respectively. Two triterpenoids, taraxasterol (1) and pseudotaraxasterol (2), one sterol, β-sitosterol (3) and one coumarin, 7-methoxycoumarin (4) were isolated from the extract. The IC50 of the mixture of compounds 1 and 2 as well as compounds 3 and 4 were higher (>100 μM) than that reported for the dichloromethane extract against MOLT-4 cells. Conclusion The dichloromethane extract was the most active one among the tested material.

The dietary flavonoids, especially their glycosides, are the most vital phytochemicals in diets and are of great general interest due to their diverse bioactivity. Almost all natural flavonoids exist as their O-glycoside or C-glycoside forms in plants. The dietary flavonoid C-glycosides have received less attention than their corresponding O-glycosides. This review summarizes current knowledge regarding flavonoid C-glycosides and their influence on human health. Among the flavonoid C-glycosides, flavone C-glycosides, especially vitexin, isoorientin, orientin, isovitexin and their multiglycosides are more frequently mentioned than others. Flavonoid C-monoglycosides are poorly absorbed in human beings with very few metabolites in urine and blood and are deglycosylated and degraded by human intestinal bacteria in colon. However, flavonoid C-multiglycosides are absorbed unchanged in the intestine and distributed to other tissues. Flavonoid C-glycosides showed significant antioxidant activity, anticancer and antitumor activity, hepatoprotective activity, anti-inflammatory activity, anti-diabetes activity, antiviral activity, antibacterial and antifungal activity, and other biological effects. It looks like that the C-glycosylflavonoids in most cases showed higher antioxidant and anti-diabetes potential than their corresponding O-glycosylflavonoids and aglycones. However, there is a lack of in vivo data on the biological benefits of flavonoid C-glycosides. It is necessary to investigate more on how flavonoid C-glycosides prevent and handle the diseases.

The 1st International Symposium on Phytochemicals in Medicine and Food (ISPMF 2015) was held in Shanghai, China, from June 26th to 29th, 2015. The 1st ISPMF was organized by the Phytochemical Society of Europe (PSE) and the Phytochemical Society of Asia (PSA). More than 270 scientists from 48 countries attended this meeting. The program of ISPMF 2015 consisted of 12 plenary lectures, 20 invited talks, and 55 short oral presentations in 16 sessions, including phytochemistry, phytomedicine, pharmacology, and application of phytochemicals in medicine and food. The 1st ISPMF has obtained support from Critical Reviews in Food Science and Nutrition, Food Chemistry, Phytochemistry Reviews, and Nutrients. As supported by Prof. Thomas F. Hofmann, a special issue on Journal of Agricultural and Food Chemistry (ACS) for the 1st ISPMF was initiated in January 2015.

Euphorbia macrostegia or Persian wood spurge is one of the seventeen endemic plants of this genus in Iran. Three triterpenoids, 24-methylenecycloartan-3β-ol (1), butyrospermol (2) and cycloartenol (3) and three diglycerides, 1,2-di-O-α-linolenoyl-sn-glycerol (4), 1-O-linoleoyl-3-O-palmitoyl-sn-glycerol (5) and 1-O-α-linolenoyl-2-O-palmitoyl-sn-glycerol (6) were isolated from the hexane soluble part of methanol-dichloromethane extracts of the aerial parts of Euphorbia macrostegia Boiss. The structures of all compounds were elucidated using different spectroscopy methods including, (1)H NMR, (13)C NMR, HSQC, HMBC, EI-MS and IR. The triterpenes and the unsaturated fatty acids moieties of the diglycerides isolated from the plant were reported previously to have analgesic, anticancer, bactericidal and antifungal activity. Here, we show that E. macrostegia is a new source for the above mentioned biologically active compounds.

The bioactive flavonoids are considered as the most important phytochemicals in food, which exert a wide range of biological benefits for human being. Microbial biotransformation strategies for production of flavonoids have attracted considerable interest because they allow yielding novel flavonoids, which do not exist in nature. In this review, we summarize the existing knowledge on the production and biotransformation of flavonoids by various microbes. The main reactions during microbial biotransformation are hydroxylation, dehydroxylation, O-methylation, O-demethylation, glycosylation, deglycosylation, dehydrogenation, hydrogenation, C ring cleavage of the benzo-γ-pyrone system, cyclization, and carbonyl reduction. Cunninghamella, Penicillium, and Aspergillus strains are very popular to biotransform flavonoids and they can perform almost all the reactions with excellent yields. Aspergillus niger is one of the most applied microorganisms in the flavonoids' biotransformation; for example, A. niger can transfer flavanone to flavan-4-ol, 2'-hydroxydihydrochalcone, flavone, 3-hydroxyflavone, 6-hydroxyflavanone, and 4'-hydroxyflavanone. The hydroxylation of flavones by microbes usually happens on the ortho position of hydroxyl group on the A ring and C-4' position of the B ring and microbes commonly hydroxylate flavonols at the C-8 position. The microorganisms tend to hydroxylate flavanones at the C-5, 6, and 4' positions; however, for prenylated flavanones, dihydroxylation often takes place on the C4α=C5α double bond on the prenyl group (the side chain of A ring). Isoflavones are usually hydroxylated at the C-3' position of the B ring by microorganisms. The microbes convert flavonoids to their 7-O-glycosides and 3-O-glycosides (when flavonoids have a hydroxyl moiety at the C-3 position). The demethylation of multimethoxyl flavonoids by microbes tends to happen at the C-3' and C-4' positions of the B ring. Multimethoxyl flavanones and isoflavone are demethylated at the C-7 and C-4' positions. The O-methylation of flavonols happens at the C-3' and C-4' and microorganisms O-methylate flavones at the C-6 position and the O-methylation of flavanones, usually took place on the hydroxyl groups of the A ring. The prenyl flavanones were cyclized at the prenyl side chain to form a new five-member ring attached to the A ring. Chalcones were regioselectively cyclized to flavanones. Hydrogenation of flavonoids was only reported on transformation of chalcones to dihydrochalcones. The dehydrogenation of flavanoids to flavonoids was not comprehensively studied., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Context: Finding effective therapies for neurodegenerative diseases is of utmost importance for the aging population. Plants growing in Iran are rich sources of antioxidants and active phytochemicals., Objective: The protective capacity of plants, with a special focus on those with reported antioxidant or neuroprotective potential or nervous system-related applications in folk medicine, was tested against oxidative stress-induced apoptosis., Materials and Methods: Aerial parts of 20 plants including Carthamus, Salvia, and Stachys species were extracted with 80% methanol and dichloromethane and preincubated with neuronal PC12 cells for 3 h. Oxidative stress and apoptosis were induced by hydrogen peroxide (75 µM, 1 h exposure). Cell viability and intracellular reactive oxygen species (ROS) were measured by MTT and 2',7'-dichlorofluorescein-diacetate (DCFH-DA) assays, respectively, while apoptosis was determined by annexin V-FITC/propidium iodide staining by a flow cytometer., Results: Eighty percent methanol extracts of Carthamus oxyacantha Bieb. (Asteraceae), Salvia santolinifolia Boiss. (Lamiaceae), and Salvia sclarea L. (Lamiaceae) at the concentration of 100 μg/ml showed significant neuroprotection in the MTT assay by 38.7, 34.7, and 39.5%, respectively, and inhibited intracellular ROS by 48.6, 61.9, and 61.4%, respectively. The first two extracts also significantly inhibited apoptosis. Dichloromethane extracts of C. oxyacantha and Stachys pilifera Benth. (Lamiaceae) at the concentration of 25 μg/ml showed neuroprotection by 27.5 and 26.5%, respectively, and inhibited ROS by 44.5 and 39.4%, respectively., Conclusion: The above-mentioned plants seem to have important biological activities and their further study may lead to the discovery of new natural therapeutics useful against disorders such as Alzheimer and Parkinson diseases.

This article has been withdrawn at the request of the editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Context: Woundwort (Stachys) plants from the Lamiaceae family have been used in folk medicine for various purposes., Objective: This study was designed to analyze cytotoxic, antioxidant and antimicrobial activities of Stachys plants, because these fields have extensively benefited of drug discovery from natural sources., Materials and Methods: Nine Stachys plants were collected from different regions of Iran. Cytotoxic activities of methanol, 80% methanol and dichloromethane (DCM) extracts of these plants were assessed on three human cancer cell lines (HL-60, K562 and MCF-7 cells) with the MTT assay, while antioxidant and antimicrobial activities were determined on methanol extracts by DPPH and nutrient broth micro-dilution assays, respectively., Results: DCM extract of St. pilifera Benth. had the lowest IC₅₀ in three cancer cell lines ranging from 33.1 to 48.2 µg/ml, followed by the 80% methanol extract of St. persica S.G.Gmel. ex C.A.Mey. (IC₅₀ range: 62.1-104.1 µg/ml) and DCM extract of St. byzantina C. Koch (IC50 range: 62.7-131.0 µg/ml). St. byzantina. St. lavandulifolia Vahl., St. acerosa Boiss., St. obtusicrena Boiss. and St. persica showed lowest IC₅₀ values in the DPPH scavenging assay (135.1, 162.6, 164.7, 169.4 and 172.4 µg/ml, respectively), while their total phenolic contents were 23.9, 18.2, 18.6, 20.4, 27.8 mg equivalent of gallic acid in 1 g dry plant, respectively. The methanol extracts of St. byzantina and St. persica inhibited all six tested Gram-negative and Gram-positive bacterial strains., Conclusion: Various Stachys species (especially St. byzantina and St. persica) are valuable sources of natural compounds with important biological properties.

The plants of the genus Salvia synthesize several types of secondary metabolites with antimicrobial, cytotoxic, and radical scavenging activities and are used in the folk medicine of different countries. Eleven Salvia species including S. aegyptiaca, S. aethiopis, S. atropatana, S. eremophila, S. hypoleuca, S. limbata, S. nemorosa, S. santolinifolia, S. sclarea, S. syriaca, and S. xanthocheila were collected from different localities in Iran and screened for their cytotoxic activity using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. The antioxidant potential and total phenol contents of the plant extracts were assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and Folin- Ciocalteu reagent respectively and finally antimicrobial activity of the above extracts were determined by using agar disc diffusion (ADD) and nutrient broth micro-dilution (NBMD) bioassays. Cytotoxic activity of methanol, 80% methanol and dichloromethane extracts of these plants were assessed on 3 human cancer cell lines. All of the extracts of S. eremophila and S. santolinifolia were active at IC50 values of 10.5-75.2 μg extract/mL, while the methanol and dichloromethane extracts of S. limbata, S. hypoleuca and S. aethiopis showed considerable cytotoxic activity against the tested cell lines. Among the tested plants for their antioxidant activity, S. nemorosa, S. atropatana, S. santolinifolia, and S. eremophila were the most active radical scavengers with higher total phenol contents while, S. limbata, S. xanthocheila and S. aegyptiaca were the weakest ones. The methanol extracts of S. santolinifolia, S. eremophila, S. sclarea and S. limbata inhibited the growth of all tested bacterial strains.

Different solvent extracts of a red algae, Hypnea flagelliformis, and two brown algae, Cystoseira myrica and Sargassum boveanum, which were collected from the Persian Gulf coast were subjected to different bioassays, including: 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay, antibacterial and antifungal activity by thin layer chromatography (TLC)-bioautography, agar disc diffusion (ADD) and nutrient-broth micro-dilution (NBMD) bioassays. The water extracts were found to have the most antioxidant activity. The antibacterial minimum inhibitory concentrations (MIC) of the active extracts were determined for the susceptible organisms, Staphylococcus aurous and Bacillus subtilis, using NBMD bioassays. The active substances were identified as free fatty acids (FFA), by using gas chromatography-mass spectrometry (GC-MS). After derivatization to their methyl esters, their concentrations were measured by using GC- lame ionization detection (GC-FID). In addition to the fatty acids, fucosterol, cholesterol and 22-dehydroxychlosterol were detected as the major sterols in S. boveanum extract using GC-MS analyses.

Two flavones, ladanein and 6-hydroxy-5,7,4'-trimethoxyflavone and one labdane-type diterpene, ent-13-epi-manoyloxide, were isolated from an ethyl acetate-methanol extract of the aerial parts of Salvia sharifii. The compounds were purified using several chromatographic methods. Structural elucidation of the compounds was performed using their (1)H and (13)C-NMR data, EI mass and UV spectral data. The compounds have been subjected to antimicrobial, antioxidant and cytotoxic activity. The diterpene showed higher cytotoxic activity than the flavones while the later compounds were better antioxidants compared with the isolated diterpene.

The essential oils of eight Salvia species collected from different localities in Iran were analyzed by gas chromatography/mass spectrometry (GC/MS). The analytical results were compared with those previously published for related Iranian sage species in order to identify chemical markers for these species. Salvia eremophila, S. hypoleuca, and S. reuteriana are endemic, while S. atropatana, S. chloroleuca, S. santolinifolia, S. aegyptiaca, and S. macrosiphon also grow wild in neighboring countries. We categorized the Iranian Salvia species into four main chemotypes according to their essential-oil constituents: those which are dominated by 1) monoterpenes, 2) mono- and sesquiterpenes, or 3) sesquiterpenes as the major constituents, and 4) those containing low-molecular-weight acids, aldehydes, and esters, and green-leaf volatiles (GLVs). Likely due to the chemical diversity of different Salvia chemotypes, this categorization was supported by principal component analysis (PCA) for the group sampled here, but not for the values reported in the literature. We identified the following chemical markers: α-pinene, β-pinene, 1,8-cineol, linalool, and borneol in monoterpene-rich species, or β-caryophyllene, germacrene D, bicyclogermacrene, spathulenol, and caryophyllene oxide in sesquiterpene-rich species. Among these, α-pinene, β-caryophyllene, and germacrene D are the most common and abundant in the Salvia species investigated. In accordance with their close biological taxonomy, the chemical similarity of the essential oils of S. santolinifolia and S. eremophila is so high that we may consider them chemically identical., (Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.)

In the vicinity of big sagebrush (Artemisia tridentata), the growth of Nicotiana attenuata is negatively affected, in part due to the alleopathic effect of methyl jasmonate (MeJA) which is produced in large quantities by the aerial parts of sagebrush. Preliminary experiments suggested that growth-inhibiting substances were being emitted from the sagebrush roots. To identify the allelochemical secondary metabolites, we tested different root extracts in seedling growth bioassays with the naturally co-occurring native tobacco, Nicotiana attenuata, in a two-chamber Petri dish assay, optimized for tests of volatiles. Fractions rich in volatile compounds were particularly phytotoxic. We analyzed the volatiles emitted from the roots of intact Artemisia tridentata plants grown in soil, sand, and hydroponic cultures by using dynamic headspace extraction, headspace solvent-microextraction (HSME) and headspace solid-phase microextraction (HSPME), and GC-MS. Camphor, 1,8-cineol, nerol, and neryl isovalerate were phytotoxic and released as the major constituents. In addition to the phytotoxic monoterpenes, himachalenes, longifolene, caryophyllene, and acetylenic spiroethers, were found as characteristic components in the root's volatiles. The allelopathic potential of these root volatiles was compared with that of methyl jasmonate (MeJA), one of the most active compounds emitted from above-ground parts of the plant.

In the Great Basin Desert, Nicotiana obtusifolia (synonymous with Nicotiana trigonophylla) and Nicotiana attenuata co-occur, but the former is frequently less attacked by larvae of the tobacco hornworm than the latter, despite having lower nicotine and trypsin protease inhibitor defenses. Glycosides of the diterpene, 17-hydroxygeranyllinalool (HGL-DTGs) have recently been found to be important defenses of N. attenuata. Total HGL-DTG levels are 5-fold higher in N. obtusifolia than in N. attenuata, and we characterize the three major HGL-DTGs purified from N. obtusifolia leaves as: 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-17-hydroxygeranyllinalool-17-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranoside; nicotinoside III and its malonic acid conjugates. Using APCI- and ESI-LC-MS, we also identified mono- and diacetyl-nicotinoside III and quercetin glycosides. To evaluate the defensive value of these HGL-DTGs, we used virus-induced-gene silencing to reduce the transcript levels of geranylgeranyl diphosphate synthase and total HGL-DTG levels in both species. When fed on silenced plants, larvae gained up to about two times more mass than those that fed on empty vector control plants of both species. We conclude that HGL-DTGs function as the most important direct defenses for both N. attenuata and N. obtusifolia., (2010 Elsevier Ltd. All rights reserved.)

We identified 11 17-hydroxygeranyllinalool diterpene glycosides (HGL-DTGs) that occur in concentrations equivalent to starch (mg/g fresh mass) in aboveground tissues of coyote tobacco (Nicotiana attenuata) and differ in their sugar moieties and malonyl sugar esters (0-2). Concentrations of HGL-DTGs, particularly malonylated compounds, are highest in young and reproductive tissues. Within a tissue, herbivore elicitation changes concentrations and biosynthetic kinetics of individual compounds. Using stably transformed N. attenuata plants silenced in jasmonate production and perception, or production of N. attenuata Hyp-rich glycopeptide systemin precursor by RNA interference, we identified malonylation as the key biosynthetic step regulated by herbivory and jasmonate signaling. We stably silenced N. attenuata geranylgeranyl diphosphate synthase (ggpps) to reduce precursors for the HGL-DTG skeleton, resulting in reduced total HGL-DTGs and greater vulnerability to native herbivores in the field. Larvae of the specialist tobacco hornworm (Manduca sexta) grew up to 10 times as large on ggpps silenced plants, and silenced plants suffered significantly more damage from herbivores in N. attenuata's native habitat than did wild-type plants. We propose that high concentrations of HGL-DTGs effectively defend valuable tissues against herbivores and that malonylation may play an important role in regulating the distribution and storage of HGL-DTGs in plants.

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.

Inhibition of Bacillus pasteurii urease enzyme by 3,7,15-tri-O-acetyl-5-O-nicotinoyl-13,14-dihydroxymyrsinol (1), a diterpene ester with a myrsinol-type skeleton, isolated from Euphorbia decipiens Boiss. and Buhse, was un-competitive consistent with the molecular docking results. The Ki value was 117.40 +/- 0.7 microM.

The chemical constituents of some species of Euphorbia, which grow mostly in semi-desert areas in Iran and on the Alborz Mountains in the north of Tehran, have been found to include chemotaxonomically important myrsinane diterpenoids and cycloartane triterpenoids. The Euphorbia plants collected in province of Azarbaijan in the northwestern part of Iran contained mostly derivatives of skin-irritating ingenol esters. Some of the diterpenoids with myrsinane carbon skeleton inhibited enzymes such as alpha-glycosidase, urease, HIV-1 reverse transcriptase, and prolyl endopeptidase. They also showed analgesic and DNA-damaging activities. The present review describes the chemistry and biological activity of several compounds isolated from different species of Iranian Euphorbia: diterpenoids with myrsinane skeletons, flavonoids, tannins, alkanes, sterols, mono-, sesqui- and triterpenoids, skin-irritating and tumor-promoting latexes and their active ingenol diterpenoids.

Two naphthoquinone diterpenoids, 1 and 2, one tricyclic, and one tetracyclic rearranged abietane ('4,5-seco-10,5-friedo-abietane') diterpenoids, 3 and 4, respectively, together with horminone (5) have been isolated from the roots of Salvia sahendica. Compounds 2 and 3 are new, and the 13C-NMR assignment for compound 4 was modified using ' Heteronuclear Multiple-Bond Correlation' (HMBC) spectroscopic data. The structures of the compounds have been established by using different spectral data including 1D- and 2D-NMR, IR, UV, and MS. The elemental composition for the major peaks of 3 and 4 were determined by ' High-Resolution Electron Impact Mass Spectrometry' (HR-EI-MS). The relative configurations of the new compounds were determined by 1H-NMR and 'Rotating-Frame NOES' (ROESY) spectroscopy. Compounds 1, 2, and 5 showed antifungal activities when tested on Blakeslea trispora. Lapachol, a prelynated naphthoquinone, was used as a positive control. The biological activities of the related naphthoquinones and abietane diterpenoids were discussed.

Three new sesquiterpene hemiacetals, tentatively named as achilleanone (1), vermiculone (2) and vermicularone (3) have been isolated from Achillea vermicularis, along with three other known compounds beta-amyrin, oleonolic acid and beta-sitosterol. The structure elucidation of new compounds was based primarily on two-dimensional (2D) NMR techniques including Nuclear Overhauser Effect/Enhancement (NOE), heteronuclear multiple quantum coherence (HMQC), heteronuclear multiple bond correlation (HMBC) and nuclear overhauser effect spectroscopy (NOESY) experiments. Compounds 1, 2 and 3 have displayed inhibitory potential against lipoxygenase enzyme in a concentration-dependent fashion with promising IC50 values.

One myrsinol-type diterpene ester (1) isolated from Euphorbia decipiens was evaluated for analgesic activity in the acetic acid induced writhing test in mice. Different dose (5-20 mg/kg i.p.) of the compound showed significant antinociceptive activity, which was comparable to standard analgesic drugs, aspirin and ibuprofen (100 mg/kg i.p.).