The journey of boswellic acids from synthesis to pharmacological activities.

There has been a lot of interest in using naturally occurring substances to treat a wide variety of chronic disorders in recent years. From the gum resin of Boswellia serrata and Boswellia carteri, the pentacyclic triterpene molecules known as boswellic acid (BA) are extracted. We aimed to provide a detailed overview of the origins, chemistry, synthetic derivatives, pharmacokinetic, and biological activity of numerous Boswellia species and their derivatives. The literature searched for reports of B. serrata and isolated BAs having anti-cancer, anti-microbial, anti-inflammatory, anti-arthritic, hypolipidemic, immunomodulatory, anti-diabetic, hepatoprotective, anti-asthmatic, and clastogenic activities. Our results revealed that the cytotoxic and anticancer effects of B. serrata refer to its triterpenoid component, including BAs. Three-O-acetyl-11-keto-BA was the most promising cytotoxic molecule among tested substances. Activation of caspases, upregulation of Bax expression, downregulation of nuclear factor-kappa B (NF-kB), and stimulation of poly (ADP)-ribose polymerase (PARP) cleavage are the primary mechanisms responsible for cytotoxic and antitumor effects. Evidence suggests that BAs have shown promise in combating a wide range of debilitating disease conditions, including cancer, hepatic, inflammatory, and neurological disorders.

Antidiabetic activity of Ipomoea cairica (L.) Sweet leaves: in-vitro and in-silico antidiabetic potential of isolated flavonoid glycosides and sulphated flavonoids.

Antidiabetic activity of methanolic extract, petroleum ether, ethyl acetate and n-butanol fractions of Ipomoea cairica (L.) Sweet leaves was performed in-vitro using α-glucosidase and α-amylase inhibition methods. Phytochemical study of the ethyl acetate fraction which possessed the highest antidiabetic activity led to isolation of five flavonoids for the first time from this plant, including two rare flavonoid sulphates, ombuin-3-sulphate [1] and rhamnetin-3-sulphate [2] and three flavonoid glycosides, kaempferol 7-O-α-L-rhamnopyranoside [3], kaempferol 3,7-di-O-α-L-rhamnopyranoside [4] and quercetin 3-O-α-L-arabinopyranoside [5]. The 1H and 13C NMR of 1 and 13C NMR of 2, were reported here for the first time. Compounds [1-4] showed a concentration-dependent in-vitro inhibitory activity against α-glucosidase and α-amylase. Furthermore, in-silico study predicted that compounds (1-5) showed good interactions with α-glucosidase, α-amylase, and protein tyrosine phosphatase 1b.

Isolation, Characterization, Complete Structural Assignment, and Anticancer Activities of the Methoxylated Flavonoids from Rhamnus disperma Roots.

Different chromatographic methods including reversed-phase HPLC led to the isolation and purification of three O-methylated flavonoids; 5,4'-dihydroxy-3,6,7-tri-O-methyl flavone (penduletin) (1), 5,3'-dihydroxy-3,6,7,4',5'-penta-O-methyl flavone (2), and 5-hydroxy-3,6,7,3',4',5'-hexa-O-methyl flavone (3) from Rhamnus disperma roots. Additionlly, four flavonoid glycosides; kampferol 7-O-α-L-rhamnopyranoside (4), isorhamnetin-3-O-ß-D-glucopyranoside (5), quercetin 7-O-α-L-rhamnopyranoside (6), and kampferol 3, 7-di-O-α-L-rhamnopyranoside (7) along with benzyl-O-ß-D-glucopyranoside (8) were successfully isolated. Complete structure characterization of these compounds was assigned based on NMR spectroscopic data, MS analyses, and comparison with the literature. The O-methyl protons and carbons of the three O-methylated flavonoids (1-3) were unambiguously assigned based on 2D NMR data. The occurrence of compounds 1, 4, 5, and 8 in Rhamnus disperma is was reported here for the first time. Compound 3 was acetylated at 5-OH position to give 5-O-acetyl-3,6,7,3',4',5'-hexa-O-methyl flavone (9). Compound 1 exhibited the highest cytotoxic activity against MCF 7, A2780, and HT29 cancer cell lines with IC50 values at 2.17 µM, 0.53 µM, and 2.16 µM, respectively, and was 2-9 folds more selective against tested cancer cell lines compared to the normal human fetal lung fibroblasts (MRC5). It also doubled MCF 7 apoptotic populations and caused G1 cell cycle arrest. The acetylated compound 9 exhibited cytotoxic activity against MCF 7 and HT29 cancer cell lines with IC50 values at 2.19 µM and 3.18 µM, respectively, and was 6-8 folds more cytotoxic to tested cancer cell lines compared to the MRC5 cells.

Roles of Suaeda vermiculata Aqueous-Ethanolic Extract, Its Subsequent Fractions, and the Isolated Compounds in Hepatoprotection against Paracetamol-Induced Toxicity as Compared to Silymarin.

Suaeda vermiculata, a halophyte consumed by livestock, is also used by Bedouins to manage liver disorders. The aqueous-ethanolic extract of S. vermiculata, its subsequent fractions, and pure compounds, i.e., pheophytin-A (1), isorhamnetin-3-O-rutinoside (2), and quercetin (3), were evaluated for their hepatoprotective efficacy. The male mice were daily fed with either silymarin, plant aq.-ethanolic extract, fractions, pure isolated compounds, or carboxyl methylcellulose (CMC) for 7 days (n = 6/group, p.o.). On the day 7th of the administrations, all, except the intact animal groups, were induced with hepatotoxicity using paracetamol (PCM, 300 mg/kg). The anesthetized animals were euthanized after 24 h; blood and liver tissues were collected and analysed. The serum aspartate transaminase (AST) and alanine transaminase (ALT) levels decreased significantly for all the S. vermiculata aq.-ethanolic extract, fraction, and compound-treated groups when equated with the PCM group (p < 0.0001). The antioxidant, superoxide dismutase (SOD), increased significantly (p < 0.05) for the silymarin-, n-hexane-, and quercetin-fed groups. Similarly, the catalase (CAT) enzyme level significantly increased for all the groups, except for the compound 2-treated group as compared to the CMC group. Also, the glutathione reductase (GR) levels were significantly increased for the n-butanol treated group than for the PCM group. The oxidative stress biomarkers, lipid peroxide (LP) and nitric oxide (NO), the inflammatory markers, IL-6 and TNF-α, and the kidney's functional biomarker parameters remained unchanged and did not differ significantly for the treated groups in comparison to the PCM-induced toxicity bearing animals. All the treated groups demonstrated significant decreases in cholesterol levels as compared to the PCM group, indicating hepatoprotective and antioxidant effects. The quercetin-treated group demonstrated significant improvement in triglyceride level. The S. vermiculata aq.-ethanolic extract, fractions, and the isolated compounds demonstrated their hepatoprotective and antioxidant effects, confirming the claimed traditional use of the herb as a liver protectant.

Isolation, characterization, anti-MRSA evaluation, and in-silico multi-target anti-microbial validations of actinomycin X2 and actinomycin D produced by novel Streptomyces smyrnaeus UKAQ_23.

Streptomyces smyrnaeus UKAQ_23, isolated from the mangrove-sediment, collected from Jubail,Saudi Arabia, exhibited substantial antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), including non-MRSA Gram-positive test bacteria. The novel isolate, under laboratory-scale conditions, produced the highest yield (561.3 ± 0.3 mg/kg fermented agar) of antimicrobial compounds in modified ISP-4 agar at pH 6.5, temperature 35 °C, inoculum 5% v/w, agar 1.5% w/v, and an incubation period of 7 days. The two major compounds, K1 and K2, were isolated from fermented medium and identified as Actinomycin X2 and Actinomycin D, respectively, based on their structural analysis. The antimicrobial screening showed that Actinomycin X2 had the highest antimicrobial activity compared to Actinomycin D, and the actinomycins-mixture (X2:D, 1:1, w/w) against MRSA and non-MRSA Gram-positive test bacteria, at 5 µg/disc concentrations. The MIC of Actinomycin X2 ranged from 1.56-12.5 µg/ml for non-MRSA and 3.125-12.5 µg/ml for MRSA test bacteria. An in-silico molecular docking demonstrated isoleucyl tRNA synthetase as the most-favored antimicrobial protein target for both actinomycins, X2 and D, while the penicillin-binding protein-1a, was the least-favorable target-protein. In conclusion, Streptomyces smyrnaeus UKAQ_23 emerged as a promising source of Actinomycin X2 with the potential to be scaled up for industrial production, which could benefit the pharmaceutical industry.

Phytochemical Characterization, In Vitro Anti-Inflammatory, Anti-Diabetic, and Cytotoxic Activities of the Edible Aromatic Plant; Pulicaria jaubertii.

Pulicaria jaubertii is a medicinal herb that alleviates inflammations and fever. Chromatographic separation, phytochemical characterization, and in vitro biological activities of the plant n-hexane extract were conducted for the first time in this study. Six compounds were isolated for the first time from the n-hexane fraction of Pulicaria jaubertii aerial parts and were identified on the bases of NMR and MS analyses as pseudo-taraxaterol (1), pseudo-taraxasterol acetate (2), 3ß-acetoxytaraxaster-20-en-30-aldehyde (3), calenduladiol-3-O-palmitate (4), stigmasterol (5), and α-tocospiro B (6). Compound (6) was a rare tocopherol-related compound and was isolated for the first time from family Asteraceae, while compound (3) was isolated for the first time from genus Pulicaria. The total alcoholic extract and n-hexane fraction were tested for their anti-inflammatory, antidiabetic, and cytotoxic activities. The n-hexane fraction has dose dependent red blood cells (RBCs) membrane stabilization and inhibition of histamine release activities with IC50: 60.8 and 72.9 µg/mL, respectively. As antidiabetic activity, the alcoholic extract exerted the most inhibition on the activity of yeast α-glucosidase, with an IC50: 76.8 µg/mL. The n-hexane fraction showed cytotoxic activity against hepatocarcinoma (HepG-2), breast carcinoma (MCF-7), and prostate carcinoma (PC-3) cell lines with IC50: 51.8, 90.8 and 62.2 µg/mL, respectively. In conclusion, the anti-inflammatory effect of Pulicaria jaubertii might be attributed to the triterpenoid constituents of the n-hexane extract of the plant.

New Phytochemical Constituent and Bioactivities of Horwoodia dicksoniae and Rumex cyprius.

BACKGROUND: Many plants growing in Saudi Arabia are used in folk medicine for treatment of several diseases. OBJECTIVE: Information of the chemical constituents and biological activities of plants is desirable for the discovery of therapeutic agents and discovering the actual value of folkloric remedies. MATERIALS AND METHODS: The compounds were isolated and purified using silica gel column chromatography and preparative high-performance liquid chromatography-diode array detector (HPLC-DAD) Method. The alcoholic extracts of these plants were evaluated for biological activities. RESULTS: Isolation and characterization of 1-feruloyl-ß-D-glucopyranoside (1) as well as new secondary metabolite tryptophan methyl ester (2) were isolated for the 1(st) time from the Horwoodia dicksoniae. The three flavones were isolated from Rumex cyprius identified as isoorientin (3), vitexin (4), and Cynarosid (5). The structures of these compounds were characterized by nuclear magnetic resonance and mass spectrometry analysis and comparing with literature. The compounds were isolated and purified using silica gel column chromatography and preparative HPLC-DAD Method. The alcoholic extracts of these plants were evaluated for antimicrobial activities against two Gram-positive bacteria, two Gram-negative bacteria, and four pathogenic fungi. Both plants showed good activities against Syncephalastrum racemosum and Streptococcus pneumoniae with minimal inhibitory concentrations (MICs) 0.98 and 1.95 µg/mL, respectively. H. dicksoniae showed good activity against Aspergillus fumigates with an MIC 1.95 µg/mL. The two extracts showed also effective free radical scavenging activities in the 1,1-diphenyl-2-picrylhydrazyl assay. H. dicksoniae exhibited remarkable cytotoxic activity against Human breast cancer mammary cancer cells-7, Human liver cancer human hepatoma carcinoma cells-2, and human lung carcinoma (A-549) cell lines. CONCLUSIONS: It was suggested that further work should be carried out to isolate, purify, and characterize the active constituents responsible for the activity of these plants. SUMMARY: New secondary metabolite Tryptophane methyl ester as well as 1-feruloyl-ß-D-glucopyranoside were isolated for the first time from the HD.Isoorientin, vitexin and Cynarosid were isolated from RC.HD exhibited good activity against Aspergillus fumigates with an MIC 1.95 µg mL(-1).HD showed significant cytotoxic activity against Human breast cancer (MCF-7), Human liver cancer (HepG-2) and Human lung carcinoma (A-549) cell lines.

A new monoterpene glucoside and complete assignments of dihydroflavonols of Pulicaria jaubertii: potential cytotoxic and blood pressure lowering activity.

One new monoterpene glucoside and five dihydroflavonols were isolated for the first time from the aerial parts of Pulicaria jaubertii and identified as p-menthane-2-O-ß-D-glucopyranoside [1], dihydroquercetin (taxifolin) [2], 7,3'-di-O-methyltaxifolin [3], 3'-O-methyltaxifolin [4], 7-O-methyltaxifolin (padmatin) [5] and 7-O-methyl-dihydrokampferol (7-O-methylaromadenderin) [6]. The structures of these compounds were unambiguously assigned on the basis of NMR spectroscopic data ((1)H, (13)C, DEPT, HSQC, HMBC) and MS analysis. 2D-NMR methods required revision of assignments of H-6 and H-8 for dihydroflavonol compounds. Possible cytotoxic activity as well as blood pressure (BP) lowering activity were tested. The alcoholic extract showed cytotoxic activity against prostate carcinoma (PC-3), breast carcinoma (MCF-7) and hepatocellular carcinoma (HepG-2) human cell lines with IC50 19.1, 20.0 and 24.1 µg, respectively. The higher dose levels of the alcoholic extract significantly reduced normal BP of rats in a dose-dependent manner.