New sterols from the South China Sea sponges Halichondria sp.

A detailed chemical investigation of two specimen of South China Sea sponges Halichondria sp. (No. 19-XD-47 and No. 17-XD-87) have resulted in the isolation of three new sterols, namely, halichsterols A (1), B (2) and C (3), together with seven related known ones (4-10). Their structures were determined by extensive spectroscopic analysis and by comparison with the spectral data reported in the literature. In bioassay, compound 2 displayed significantly anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells.

Therapeutic attributes and applied aspects of biological macromolecules (polypeptides, fucoxanthin, sterols, fatty acids, polysaccharides, and polyphenols) from diatoms - A review.

Diatoms are ubiquitous, biologically widespread, and have global significance due to their unique silica cell wall composition and noteworthy applied aspects. Diatoms are being extensively exploited for environmental monitoring, reconstruction, and stratigraphic correlation. However, considering all the rich elements of diatoms biology, the current literature lacks sufficient information on the therapeutic attributes and applied aspects of biological macromolecules from diatoms, hampering added advances in all aspects of diatom biology. Diatoms offer numerous high-value compounds, such as fatty acids, polysaccharides, polypeptides, pigments, and polyphenols. Diatoms with a high content of PUFA's are targets of transformation into high-value products through microalgal technologies due to their wide application and growing market as nutraceuticals and food supplements. Diatoms are renewable biomaterial, which can be used to develop drug delivery systems due to biocompatibility, surface area, cost-effective ratio, and ease in surface modifications. Innovative approaches are needed to envisage cost-effective ways for the isolation of bioactive compounds, enhance productivity, and elucidate the detailed mechanism of action. This review spotlights the notable applications of diatoms and their biologically active constituents, such as fucoxanthin and omega 3 fatty acids, among others with unique structural and functional entities.

Network pharmacology of bioactives from Sorghum bicolor with targets related to diabetes mellitus.

BACKGROUND: Sorghum bicolor (SB) is rich in protective phytoconstituents with health benefits and regarded as a promising source of natural anti-diabetic substance. However, its comprehensive bioactive compound(s) and mechanism(s) against type-2 diabetes mellitus (T2DM) have not been exposed. Hence, we implemented network pharmacology to identify its key compounds and mechanism(s) against T2DM. METHODS: Compounds in SB were explored through GC-MS and screened by Lipinski's rule. Genes associated with the selected compounds or T2DM were extracted from public databases, and the overlapping genes between SB-compound related genes and T2DM target genes were identified using Venn diagram. Then, the networking between selected compounds and overlapping genes was constructed, visualized, and analyzed by RStudio. Finally, affinity between compounds and genes was evaluated via molecular docking. RESULTS: GC-MS analysis of SB detected a total of 20 compounds which were accepted by the Lipinski's rule. A total number of 16 compounds-related genes and T2DM-related genes (4,763) were identified, and 81 overlapping genes between them were selected. Gene set enrichment analysis exhibited that the mechanisms of SB against T2DM were associated with 12 signaling pathways, and the key mechanism might be to control blood glucose level by activating PPAR signaling pathway. Furthermore, the highest affinities were noted between four main compounds and six genes (FABP3-Propyleneglyco monoleate, FABP4-25-Oxo-27-norcholesterol, NR1H3-Campesterol, PPARA-ß-sitosterol, PPARD-ß-sitosterol, and PPARG-ß-sitosterol). CONCLUSION: Our study overall suggests that the four key compounds detected in SB might ameliorate T2DM severity by activating the PPAR signaling pathway.

Cytotoxic polyhydroxy sterols from the Egyptian Red Sea soft coral Sarcophyton acutum.

The methanolic extract and its sub-extracts (viz, n-hexane, DCM, EtOAc and MeOH) of the soft coral Sarcophyton acutum were evaluated as anti-Leishmania major and as anticancer (against the HepG2, MCF-7, and A549 cell lines) using the MTT assay. Six polyhydroxy sterols (1-6) were isolated from the most active cytotoxic and anti-leishmanial EtOAc-soluble fraction. Their structures were established as two new polyhydroxy sterols, acutumosterols A (1) and B (2), and four known structural analogues (3-6) by intensive spectroscopic analyses, and by comparison with data of related compounds. Compound 4 exerted noticeable cytotoxicity against HepG2 cell line (IC50 17.2 ± 1.5 µg/mL), while the other pure isolates showed weak to moderate cytotoxicity (24.8 ± 2.8-57.2 ± 5.2). The results were discussed in relation to the structural features of these closely related sterols.

Cichorins D-F: Three New Compounds from Cichorium intybus and Their Biological Effects.

Cichorium intybus L., (chicory) is employed in various traditional medicines to treat a wide range of diseases and disorders. In the current investigation, two new naphthalane derivatives viz., cichorins D (1) and E (2), along with one new anthraquinone cichorin F (3), were isolated from Cichorium intybus. In addition, three previously reported compounds viz., ß-sitosterol (4), ß-sitosterol ß-glucopyranoside (5), and stigmasterol (6) were also isolated from Cichorium intybus. Their structures were established via extensive spectroscopic data, including 1D (1H and 13C) and 2D NMR (COSY, HSQC and HMBC), and ESIMS. Cichorin E (2) has a weak cytotoxic effect on breast cancer cells (MDA-MB-468: IC50: 85.9 µM) and Ewing's sarcoma cells (SK-N-MC: IC50: 71.1 µM); cichorin F (3) also illustrated weak cytotoxic effects on breast cancer cells (MDA-MB-468: IC50: 41.0 µM and MDA-MB-231: IC50: 45.6 µM), and SK-N-MC cells (IC50: 71.9 µM). Moreover compounds 1-3 did not show any promising anthelmintic effects.

Anti-arthritic and anti- inflammatory effects of extract and fractions of Malva parviflora in a mono- arthritis model induced with kaolin/carrageenan.

Malva parviflora is used as food in the gastronomy of some regions of Mexico and, also, in Mexican traditional medicine for inflammation-related conditions like rheumatoid arthritis. The objective of this work was to evaluate its antiarthritic activity in a mice model. In ICR, female mice were tested the dichloromethane extract (MpD) and fractions MpF4 (extracted with a dichoromethane:methanol system) and MpFphy (a precipitate by acetone:methanol) by using the mono-arthritis with kaolin/carrageenan model. During the treatment, joint inflammation was measured daily, and hyperalgesia was measured using the hot plate test. The treatments diminished both joint inflammation and pain. At the end of the evaluation, the left joint and spleen were extracted for determination of pro- and anti-inflammatory cytokines. The results showed that the MpD, MpF4, and MpFphy treatments modulated the concentration of these proteins. Specifically, MpFphy at 1.0 mg/kg increased IL-4 and IL-10 and decreased IL-17, IL-1ß, and TNF-α. GC-MS analysis showed that MpF4 contained a mixture of a total of nine compounds, three of them newly reported for the species. The studies confirmed the presence of five sterols in the MpFphy fraction, including stigmasterol and ß-sitosterol. These results confirm the anti-rheumatoid and anti-inflammatory activities of a fraction rich in sterols from Malva parviflora. Graphical abstract.

Hypolipidemic potential of sterol containing fractions of Jolyna laminarioides: a brown alga.

Solvent fractions (n-hexane, cholorofrom, methanol) and fractions containing sterols of Jolyna laminarioides was evaluated in triton-induced and high-fat-diet induced hyperlipidemic rats. Oral administration of J. laminarioides significantly reduced the elevated level of serum total cholesterol, triglycerides and LDL-c, both in triton induced and high fat diet induced hyperlipidemic rat models with increased serum HDL-c. Chloroform: methanol fraction (2:1) and n-hexane fraction containing sterol showed promising results in reducing LDL-c. The methanol fraction showed hypolipidemic effect by increasing HDL-c (90%). The extracts and fractions of the seaweed also decreased the increased level of cardiac and hepatic marker enzymes beside lowering lipid profile. J. laminarioides exhibited high anti-hyperlipidemic effects both in triton induced and high fat diet induced hyperlipidemic rats.

Tephrosia apollinea seed: a new rich source of essential polyunsaturated fatty acids, tocopherols, sterols, and squalene.

Tephrosia apollinea is a legume species, native to southwest Asia and northeast Africa, rich in bioactive flavonoids (hydrophilic compounds). T. apollinea seeds were not considered previously as a potential source of lipophilic compounds such as: essential fatty acids, tocopherols, sterols, and squalene, hence, the present study were performed. The oil yield in T. apollinea seeds amounted to 11.8% dw. The T. apollinea seed oil was predominated by the polyunsaturated fatty acids - linoleic (26.8%) and α-linolenic (22.7%). High levels were recorded also for oleic (27.6%) and palmitic (14.9%) acids. Four tocopherols and one tocotrienol, with the domination of γ-tocopherol (98%) were identified in T. apollinea seed oil. The ß-sitosterol (59%), Δ5-stigmasterol (21%) and campesterol (9%) were detected as main sterols in T. apollinea seed oil. The total content of tocochromanols, sterols, carotenoids and squalene in the T. apollinea seed oil was 256.7, 338.1, 12.5 and 1103.8 mg/100 g oil, respectively. T. apollinea seeds oil, due to the high concentration of lipophilic bioactive compounds can find a potential application in the food, cosmetic and pharmaceutical industry.

Characterization and evaluation of mycosterol secreted from endophytic strain of Gymnema sylvestre for inhibition of α-glucosidase activity.

Endophytic fungi produce various types of chemicals for establishment of niche within the host plant. Due to symbiotic association, they secrete pharmaceutically important bioactive compounds and enzyme inhibitors. In this research article, we have explored the potent α-glucosidse inhibitor (AGI) produced from Fusarium equiseti recovered from the leaf of Gymnema sylvestre through bioassay-guided fraction. This study investigated the biodiversity, phylogeny, antioxidant activity and α-glucosidse inhibition of endophytic fungi isolated from Gymnema sylvestre. A total of 32 isolates obtained were grouped into 16 genera, according to their morphology of colony and spores. A high biodiversity of endophytic fungi were observed in G. sylvestre with diversity indices. Endophytic fungal strain Fusarium equiseti was identified through DNA sequencing and the sequence was deposited in GenBank database (https://ncbi.nim.nih.gov) with acession number: MF403109. The characterization of potent compound was done by FTIR, LC-ESI-MS and NMR spectroscopic analysis with IUPAC name 17-(5-ethyl-6-methylheptan-2-yl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a] phenanthren-3-ol. The isolated bioactive compound showed significant α-amylase and α-glucosidase inhibition activity with IC50 values, 4.22 ± 0.0005 µg/mL and 69.72 ± 0.001 µg/mL while IC50 values of acarbose was 5.75 ± 0.007 and 55.29 ± 0.0005 µg/mL respectively. This result is higher in comparison to other previous study. The enzyme kinetics study revealed that bioactive compound was competitive inhibitor for α-amylase and α-glucosidase. In-silico study showed that bioactive compound binds to the binding site of α-amylase, similar to that of acarbose but with higher affinity. The study highlights the importance of endophytic fungi as an alternative source of AGI (α-glucosidase inhibition) to control the diabetic condition in vitro.

Pharmacological importance of Manilkara zapota and its bioactive constituents / Importancia farmacologica de Manilkara zapota y sus constituyentes bioactivos

Manilkara zapota (Sapotaceae), commonly known as Sapodilla, is widely known for its delicious fruit. Various parts of this plant are also used in folk medicine to treat a number of conditions including fever, pain, diarrhoea, dysentery, haemorrhage and ulcers. Scientific studies have demonstrated analgesic, anti-inflammatory, antioxidant, cytotoxic, antimicrobial, antidiarrheal, anti-hypercholesteremic, antihyperglycemic and hepatoprotective activities in several parts of the plant. Phytochemical studies have revealed the presence of phenolic compounds including protocatechuic acid quercitrin, myricitrin, catechin, gallic acid, vanillic acid, caffeic acid, syringic acid, coumaric acid, ferulic acid, etc. as main constituents of the plant. Several fatty acids, carotenoids, triterpenes, sterols, hydrocarbons and phenylethanoid compounds have also been isolated from M. zapota. The present review is a comprehensive description focused on pharmacological activities and phytochemical constituents of M. zapota.

Manilkara zapota (Sapotaceae), comúnmente conocida como Sapodilla, es ampliamente conocida por su delicioso fruto. Variadas partes de esta planta se usan en medicina popular para tratar una serie de afecciones, como fiebre, dolor, diarrea, disentería, hemorragia y úlceras. Estudios científicos han demostrado actividad analgésica, antiinflamatoria, antioxidante, citotóxica, antimicrobiana, antidiarreica, antihipercolesterolémica, antihiperglucémica y hepatoprotectora en diferentes partes de la planta. Los estudios fitoquímicos han revelado la presencia de compuestos fenólicos que incluyen ácido protocatechúico, quercitrina, miricitrina, catequina, ácido galico, ácido vanílico, ácido cafeico, ácido sirínico, ácido cumárico, ácido fúnico y ácido ferúlico como componentes principales de la planta. Varios ácidos grasos, carotenoides, triterpenos, esteroles, hidrocarburos y compuestos feniletanoides también han sido aislados de M. zapota. La presente revisión es una descripción exhaustiva centrada en las actividades farmacológicas y los constituyentes fitoquímicos de M. zapota.

New furostanol glycosides from Polygonatum multiflorum (L.) All.

The phytochemical investigation of the whole plant of Polygonatum multiflorum resulted in the isolation of two new steroidal glycosides, polmultoside A (4) and polmultoside B (5), along with three known glycosides protobioside (1), protodeltonin (2) and huangjiangsu A (3). The structures of the isolated compounds have been elucidated by extensive 1D (1H, 13C) and 2D (COSY, HSQC, HMBC) NMR spectral data analysis, as well as high-resolution mass determinations.

In vitro and in silico antimicrobial activity of sterol and flavonoid isolated from Trianthema decandra L.

Phytochemical study on the leaves of Trianthema decandra leads to the isolation and characterization of two compounds from chloroform extract. The compounds were characterized using HPLC, UV, FT-IR, NMR, LCMS and CHNS. The structure of compounds were elucidated from spectral data and named according to rules laid down in IUPAC nomenclature. A novel sterol was named as 17-(5-ethyl-6-methylheptan-2-yl) -4, 4, 10, 13-tetramethyl-hexadecahydro-1H-cyclopenta (α) phenanthren-3-ol and the flavonoid was named as 2-(3, 4 dihydroxy - phenyl)-3, 5, 7 - trihydroxy-chromen-4 one. The antimicrobial activity of sterol and flavonoid isolated from T. decandra were examined by disc diffusion and broth dilution assays. The isolated compounds showed excellent activity against all the tested microorganisms. Sterol exhibits MIC value of 39.05 µg/ml against S. typhi whereas flavonoid shows 78.10 µg/ml against V. cholerae. The plausible mode of action of these compounds was studied using in silico molecular docking with Penicillin Binding Protein (PBP) as target.

New 4-methylidene sterols from the marine sponge Theonella swinhoei.

A series of 4-methylidene sterols including three new compounds 1-3, were isolated from the marine sponge Theonella swinhoei. The structures of new compounds were determined on the basis of spectroscopic analyses. Compounds 3, 5, and 6 showed cytotoxicities against U937, MCF-7, and PC-9 cancer cells with IC50 in the range of 1.6-8.8 µM. The new compound 3 exhibited remarkable proapoptotic activity in breast cancer cells. Mechanically, 3 significantly triggered reactive oxygen species (ROS) accumulation resulting in apoptosis and DNA damage in breast cancer cells.

A Validated Reverse-Phase HPLC Method for Quantitative Determination of Ganoderic Acids A and B in Cultivated Strains of Ganoderma spp. (Agaricomycetes) Indigenous to India.

Twenty isolates of Ganoderma spp. indigenous to India were used in this study. A reverse-phase high-performance liquid chromatography (HPLC) method was used to quantify 2 of the most bioactive triterpenes, ganoderic acid A (GAA) and ganoderic acid B (GAB), among the cultivated Ganoderma spp. The HPLC analysis was performed on an Agilent 1260 Infinity HPLC system with a Zorbax C18 column, using gradient elution of acetonitrile and 0.1% acetic acid. The detection wavelength was set at 254 nm, with a flow rate of 0.6 mL/min. The method was validated according to the guidelines of International Conference on Harmonisation and produced satisfactory results. The amount of GAA varied from 827.50 to 2010.36 µg/g, whereas GAB varied from 16.64 to 916.89 µg/g. The developed method is simple, specific, accurate, and precise, and can be useful for qualitative and quantitative evaluation of ganoderic acids.

In vitro and in vivo antidiabetic potential of extracts and a furostanol saponin from Balanites aegyptiaca.

CONTEXT: Balanites aegyptiaca Del. (Zygophyllaceae) fruits are well-known antidiabetic drug in Egyptian folk medicine. Nevertheless, its mechanism of action is still unclear. OBJECTIVES: Searching for the possible mechanisms of action of the plant and identification of its bioactive compounds. MATERIALS AND METHODS: A bio-guided protocol based on the evaluation of α-glucosidase (AG) and aldose reductase (AR) inhibitory activities was adopted to isolate the biologically active compounds from the methanol extract (MeEx). An in vivo antidiabetic study was conducted for the active extract, fraction and compound using streptozotocin-induced diabetic male albino Wistar rats at two dose levels (100 and 200 mg/kg.b/wt) for 2 weeks. RESULTS: Three compounds were isolated and identified: a sterol, (1) stigmasterol-3-O-ß-d-glucopyranoside; a pregnane glucoside, (2) pregn-5-ene-3ß,16ß,20(R)-trio1-3-O-ß-d-glucopyranoside; a furostanol saponin, (3) 26-(O-ß-d-glucopyranosyl)-22-O-methylfurost-5-ene-3ß,26-diol-3-O-ß-d-glucopyranosyl-(1 → 4)-[α-l-rhamnopyranosyl-(1 → 2)]-ß-d-glucopyranoside. Only compound 3 possessed significant AG and AR inhibitory activities (IC50 = 3.12 ± 0.17 and 1.04 ± 0.02 µg/mL, respectively), while compounds 1 and 2 were inactive. The in vivo antidiabetic study revealed that MeEx and furostanol saponin 3 possessed significant activities at a dose of 200 mg/kg through reducing the fasting plasma glucose level by 46.14% and 51.39%, respectively, as well as reducing the total cholesterol by 24.44% and 31.90%, respectively. Compound 3 also caused increment in insulin and C-peptide levels by 63.56% and 65%, respectively. DISCUSSION AND CONCLUSIONS: We presented a scientific base for using Balanites aegyptiaca, and shed the light on one of its saponins, as an antidiabetic agent in fasting and postprandial hyperglycaemia along with the improvement of diabetic complications.

Chemical Composition of Laurencia obtusa Extract and Isolation of a New C15-Acetogenin.

A new C15-acetogenin, sagonenyne (20), exhibiting an unusual single tetrahydropyran ring was isolated from an ethyl acetate extract of Laurencia obtusa collected on the Corsican coastline. Its structure was established by detailed NMR spectroscopic analysis, mass spectrometry, and comparison with literature data. Twenty-three known compounds were identified in the same extract by means of column chromatography steps, using a 13C-NMR computer aided method developed in our laboratory. In addition to sesquiterpenes, which represent the main chemical class of this extract, diterpenes, sterols, and C15-acetogenins were identified. The crude extract was submitted to a cytotoxicity assay and was particularly active against THP-1 cells, a human leukemia monocytic cell line.

Chemical Characterization of Lodoicea maldivica Fruit.

In the present study, we report the attempt to characterize the chemical composition of fruit kernel of Lodoicea maldivica coco nucifera palm (commonly named as 'Coco de mer') by gas chromatographic method. The analysis was performed by HS-SPME and GC/MS techniques to determine volatile aroma, sterol, and fatty acid composition profiles in the internal and external pulp of two distinct coconuts. Although no qualitative differences in flavour composition were observed between the two analysed coconuts and the relative two pulp parts, variations in the abundance levels of the prominent compounds have been recorded. The averaged quantity of total phytosterols, resulting from the two analysed 'Coco de mer' samples, was almost constant in both kernels coconut, being 24.5 µg/g (of dry net matter) for the external, and 26.9 µg/g (of dry net matter) for the internal portion. In both coconuts, the fatty acid pattern composition was characterized by seven saturated acids ranged from C14:0 (myristic) to C20:0 (arachidic) and two monounsaturated acids, the palmitoleic (C16:1, ω7) and the oleic (C18:1, ω9). Palmitic acid (C16:0) was the predominant one with an average contribution of about 49.0%, followed by pentadecanoic 16.5%, stearic (C18:0) 11.6%, and myristic (C14:0) 9.9% acids in all two examined kernel portions.

Six new furostanol glycosides from Smilax glauco-china and their cytotoxic activity.

Six new steroidal saponins, namely glauco-chinaosides A-F, and one known compound were isolated from the tubers of Smilax glauco-china. Their structures were elucidated by a combination of spectroscopic analysis and hydrolysis followed by spectral and chromatographic analysis. Compounds 1-7 were tested in vitro for their cytotoxic activities against four human tumor cell lines (SH-SY5Y, SGC-7901, HCT-116, and Lovo). Compounds 1, 2, and 5 exhibited cytotoxic activity against SGC-7901, with IC50 values of 2.7, 11.5, and 6.8 µM, respectively.

Therapeutic Strategies of Plant-derived Compounds for Diabetes Via Regulation of Monocyte Chemoattractant Protein-1.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a member of the CC chemokine family that plays a key role in the inflammatory process. It has been broadly studied in the aspect of its role in obesity and diabetes related diseases. MCP-1 causes the infiltration of macrophages into obese adipose tissue via binding to the CCR2 receptor and is involved in the development of insulin resistance. METHODS: We reviewed the available literature regarding the importance of plant metabolites that regulate MCP-1 activity and are used in the treatment of diabetic disorders. The characteristics of screened papers were described and the important findings were included in this review. RESULTS: This mini-review provides a summary of functions and therapeutic strategies of this chemokine, with a special focus on plant-derived compounds that possess a putative antidiabetic function via a mechanism of MCP-1 interaction. The highlights of this review include the roles of MCP-1 in development of diabetes, the evaluation of plant metabolites that specifically or non-specifically inhibit MCP-1 overproduction, and the molecular mechanisms of this activity. Among these metabolites, we particularly focused on phenolic acids and their derivatives, flavonoids, stilbenes, anthocyanins, capsaicin, alkaloids, plant sterols, terpenes, saponins, unsaturated fatty acids and plant-derived extracts. CONCLUSION: Regarding the increasing number of diabetic patients yearly, the recent progress in the putative therapies needs to be summarized. This article underlines the significance and involvement of the chemokine MCP-1 in the development of obesity, type 2 diabetes, and diabetic complications, with an emphasis on the role of plant metabolites in the regulation of this chemokine and thus the role in the prevention or therapy of diabetes. We suggest that MCP-1 might be a molecular marker of type 2 diabetes.

Anti-complementary constituents of Viola kunawarensis.

Activity-guided fractionation for complement inhibitors led to the isolation of 22 known compounds from Viola kunawarensis. Chemical types include six sterol compounds, three coumarin compounds, five megastigmane compounds, two triterpenoid compounds, two phenylpropanoid compounds, one chlorophyll, one amide, and two lipid compounds. Among which, two sterols (stigmasta-4-ene-3ß,6ß-diol and saringosterone), one amide (aurantiamide acetate) and a norsesquiterpenoid (solalyratin B) exhibited better anti-complementary effects with CH50 values ranging from 0.02 to 0.08 mM, which are plausible candidates for developing potent anti-complementary agents.