Cytotoxic effects of extracts obtained from plants of the Oleaceae family: bio-guided isolation and molecular docking of new secoiridoids from Jasminum humile.

CONTEXT: Traditionally, Oleaceae plants are used to treat many diseases, such as rheumatism, hypercholesterolaemia, or ulcers. OBJECTIVES: To investigate the cytotoxic potential of Jasminum humile L., Jasminum grandiflorum L., and Olea europaea L. (Oleaceae) extracts against selected human cancer cells lines, followed by a phytochemical investigation of the most potent one. MATERIALS AND METHODS: The 95% ethanol extracts of aerial parts of three oleaceous plants were examined for their cytotoxicity against HepG-2, MCF-7, and THP-1 cell lines using MTT assay and doxorubicin (positive control). J. humile was bio-selected and submitted to bio-guided fractionation. Chromatographic workup of ethyl acetate and n-butanol fractions afforded two new compounds; 1-methoxyjasmigenin (1) and 1-methyl-9-aldojasmigenin (2), along with five known ones (3-7). Structures were unambiguously elucidated using 1D/2D NMR and ESI-HRMS. Isolated compounds were assessed for their anti-proliferative potential, and both selectivity index and statistical significance were determined. Molecular docking was conducted against the Mcl-1 receptor using (AZD5991) as a standard. RESULTS: Jasmoside (5) was the most potent anticancer compound showing IC50 values of 66.47, 41.32, and 27.59 µg/mL against HepG-2, MCF-7, and THP-1 cell lines, respectively. Moreover, isojasminin (4) exhibited IC50 values of 33.49, 43.12, and 51.07 µg/mL against the same cell lines, respectively. Interestingly, 5 exhibited the highest selectivity index towards MCF-7 and THP-1, even greater than doxorubicin. Molecular docking results were in full agreement with the MTT assay and the proposed SAR. CONCLUSION: In this study, two new compounds were purified. The biological activity highlighted jasmoside (5) as a lead anticancer drug for further future investigation.

In vitro and in silico studies of SARS-CoV-2 main protease Mpro inhibitors isolated from Helichrysum bracteatum.

Discovering SARS-CoV-2 inhibitors from natural sources is still a target that has captured the interest of many researchers. In this study, the compounds (1-18) present in the methanolic extract of Helichrysum bracteatum were isolated, identified, and their in vitro inhibitory activities against SARS-CoV-2 main protease (Mpro) was evaluated using fluorescence resonance energy transfer assay (FRET-based assay). Based on 1D and 2D spectroscopic techniques, compounds (1-18) were identified as 24-ß-ethyl-cholesta-5(6),22(23),25(26)-triene-3-ol (1), α-amyrin (2), linoleic acid (3), 24-ß-ethyl-cholesta-5(6),22(23),25(26)-triene-3-O-ß-d-glucoside (4), 1,3-propanediol-2-amino-1-(3',4'-methylenedioxyphenyl) (5), (-)-(7R,8R,8'R)-acuminatolide (6), (+)-piperitol (7), 5,7,4'-trihydroxy-8,3'-dimethoxy flavanone (8), 5,7,4'-trihydroxy-6-methoxy flavanone (9), 4',5-dihydroxy-3',7,8-trimethoxyflavone (10), 5,7-dihydroxy-3',4',5',8-tetramethoxy flavone (11), 1,3-propanediol-2-amino-1-(4'-hydroxy-3'-methoxyphenyl) (12), 3',5',5,7-tetrahydroxy-6-methoxyflavanone (13), simplexoside (piperitol-O-ß-d-glucoside) (14), pinoresinol monomethyl ether-ß-d-glucoside (15), orientin (16), luteolin-3'-O-ß-d-glucoside (17), and 3,5-dicaffeoylquinic acid (18). Compounds 6, 12, and 14 showed comparable inhibitory activities against SARS-CoV-2 Mpro with IC50 values of 0.917 ± 0.05, 0.476 ± 0.02, and 0.610 ± 0.03 µM, respectively, compared with the control lopinavir with an IC50 value of 0.225 ± 0.01 µM. The other tested compounds showed considerable inhibitory activities. The molecular docking study for the tested compounds was carried out to correlate their binding modes and affinities for the SARS-CoV-2 Mpro enzyme with the in vitro results. Analyzing the results of the in vitro assay together with the obtained in silico results led to the conclusion that phenylpropanoids, lignans, and flavonoids could be considered suitable drug leads for developing anti-COVID-19 therapeutics. Moreover, the phenylpropanoid skeleton oxygenated at C3, C4 of the phenyl moiety and at C1, C3 of the propane parts constitute an essential core of the SARS-CoV-2 Mpro inhibitors, and thus could be proposed as a scaffold for the design of new anti-COVID-19 drugs.

Nanoemulsions of Jasminum humile L. and Jasminum grandiflorum L. Essential Oils: An Approach to Enhance Their Cytotoxic and Antiviral Effects.

Unprecedented nanoemulsion formulations (NE) of Jasminum humile and Jasminum grandiflorum essential oils (EO) were prepared, and examined for their cytotoxic and antiviral activities. NE characterization and stability examination tests were performed to ensure formula stability. The antiviral activity was determined against hepatitis A (HAV) and herpes simplex type-1 (HSV-1) viruses using MTT assay, while the cytotoxic potential was determined against liver (HepG-2), breast (MCF-7), leukemia (THP-1) cancer cell lines and normal Vero cells. Statistical significance was determined in comparison with doxorubicin as cytotoxic and acyclovir as antiviral standard drugs. GC-MS analysis indicated twenty four compounds in the EO of J. humile and seventeen compounds in the EO of J. grandiflorum. Biological investigations of pure EOs revealed weak cytotoxic and antiviral effects. Nevertheless, their NE formulations exhibited high biological value as cytotoxic and antiviral agents. NE formulations also showed feasible selectivity index for the viral-infected and cancer cells (especially HepG-2) than normal Vero cells. Both nanoemulsions showed lower IC50 than standard doxorubicin against HepG-2 (26.65 and 22.58 vs. 33.96 µg/mL) and MCF-7 (36.09 and 36.19 vs. 52.73 µg/mL), respectively. The study results showed the dramatic effect of nanoemulsion preparation on the biological activity of EOs and other liposoluble phytopharmaceuticals.

Acetylcholine esterase inhibitory activity of green synthesized nanosilver by naphthopyrones isolated from marine-derived Aspergillus niger.

Aspergillus niger metabolites exhibited a wide range of biological properties including antioxidant and neuro-protective effects and some physical properties as green synthesis of silver nanoparticles AgNP. The present study presents a novel evidence for the various biological activities of green synthesized AgNPs. For the first time, some isolated naphtho-γ-pyrones from marine-derived Aspergillus niger, flavasperone (1), rubrofusarin B (2), aurasperone A (3), fonsecinone A (4) in addition to one alkaloid aspernigrin A (7) were invistigated for their inhibitory activity of acetylcholine esterase AChE, a hallmark of Alzheimer's disease (AD). The ability to synthesize AgNPs by compounds 3, 4 and 7 has been also tested for the first time. Green synthesized AgNPs were well-dispersed, and their size was ranging from 8-30 nm in diameter, their morphology was obviously spherical capped with the organic compounds. Further biological evaluation of their AChE inhibitory activity was compared to the parent compounds. AgNps dramatically increased the inhibitory activity of Compounds 4, 3 and 7 by 84, 16 and 13 fold, respectively to be more potent than galanthamine as a positive control with IC50 value of 1.43 compared to 0.089, 0.311 and 1.53 of AgNPs of Compounds 4, 3 and 7, respectively. Also compound 2 showed moderate inhibitory activity. This is could be probably explained by closer fitting to the active sites or the synergistic effect of the stabilized AgNPs by the organic compouds. These results, in addition to other intrinsic chemical and biological properties of naphtho-γ-pyrones, suggest that the latter could be further explored with a view towards other neuroprotective studies for alleviating AD.

Antiproliferative activity of stilbene derivatives and other constituents from the stem bark of Morus nigra L.

The antiproliferative activities of 2',3,4',5,5'-pentahydroxy-cis-stilbene 1, resveratrol 2, oxyresveratrol 3, norartocarpetin 4, kuwanon C 5, morusin 6, cudraflavone A7, kuwanon G 8, albafuran C 9, mulberrofuran G 10, 3-acetyl-O-α-amyrin 11, 3-acetyl-O-ß-amyrin 12, ursolic acid-3-O-acetate 13 and uvaol 14, previously identified from the barks of Morus nigra L., were investigated against HepG2 and MCF-7 cell lines. In addition, a series of methylated stilbenes 15-19 were prepared using compounds 1-3 and their antiproliferative effects were similarly investigated. The structure of a new 2',3,4'-trimethoxy-5-hydroxy-trans-stilbene 19 was elucidated using spectroscopic techniques. It showed remarkable activity against MCF-7 cells with IC50 12.5 µM. However, kuwanon C (5) showed the highest antiproliferative activity with IC50 3.92 and 9.54 µM against MCF-7 and HepG2, respectively.

Cytotoxic constituents of Alocasia macrorrhiza.

An indole alkaloid, 2-(5-hydroxy-1H-indol-3-yl)-2-oxo-acetic acid (1) isolated for the first time from nature, in addition to the nine known compounds 5-hydroxy-1H-indole-3-carboxylic acid methyl ester (2), alocasin B (3), hyrtiosin B (4), α-monopalmitin (5), 1-O-ß-D-glucopyranosyl-(2S, 3R, 4E, 8Z)-2-[(2(R)-hydroctadecanoyl) amido]-4,8-octadecadiene-1,3-diol (6), 3-epi-betulinic acid (7), 3-epi-ursolic acid (8), ß-sitosterol (9) and ß-sitosterol 3-O-ß-D-glucoside (10) were isolated from the rhizomes of Alocasia macrorrhiza (Araceae). Their structures were elucidated by 1D and 2D NMR spectroscopic data. Of these compounds, 6 exhibited the strongest cytotoxicity against the four tested human cancer cell lines (IC50 of about 10 µM against Hep-2 larynx cancer cells).

Cardioprotective and antioxidant effects of oleogum resin "Olibanum" from Bos Boswellia carteri Birdw. (Bursearceae).

One of the leading causes of death worldwide is cardiovascular disease, hence searching for a cure is an important endeavor. The totally safe, edible, and inexpensive Boswellia plant exudate, known as olibanum or frankincense, is considered to possess diverse medicinal values in traditional medicine and from recent biological studies. Investigating the cardioprotective and antioxidant activities of olibanum from a Boswellia species, family Bursearaceae, namely Boswellia carteri Birdw. was the aim of this study. Cardioprotective activity was evaluated using a model of myocardial infarction induced by isoprenaline (ISO), while antioxidant activity was tested adopting nitric oxide scavenging (NOS) and azino-bis-3-ethyl benzthiazoline-6-sulfonic acid (ABTS) assays. The results revealed a mild cardioprotective effect and weak antioxidant activity.

Assessment of anti-quorum sensing activity for some ornamental and medicinal plants native to egypt.

This study investigated the effects of some plant extracts on the bacterial communication system, expressed as quorum sensing (QS) activity. Quorum sensing has a directly proportional effect on the amount of certain compounds, such as pigments, produced by the bacteria. Alcohol extracts of 23 ornamental and medicinal plants were tested for anti-QS activity by the Chromobacterium violaceum assay using the agar cup diffusion method. The screening revealed the anti-QS activity of six plants; namely the leaves of Adhatoda vasica Nees, Bauhinia purpurea L., Lantana camara L., Myoporum laetum G. Forst.; the fruits of Piper longum L.; and the aerial parts of Taraxacum officinale F.H. Wigg.