Platanosides from Platanus × acerifolia: New molecules, SAR, and target validation of a strong lead for drug-resistant bacterial infections and the associated sepsis.

Three undescribed (1-3) and nine known (4-12) platanosides were isolated and characterized from a bioactive extract of the May leaves of Platanus × acerifolia that initially showed inhibition against Staphylococcus aureus. Targeted compound mining was guided by an LC-MS/MS-based molecular ion networking (MoIN) strategy combined with conventional isolation procedures from a unique geographic location. The novel structures were mainly determined by 2D NMR and computational (NMR/ECD calculations) methods. Compound 1 is a rare acylated kaempferol rhamnoside possessing a truxinate unit. 6 (Z,E-platanoside) and 7 (E,E-platanoside) were confirmed to have remarkable inhibitory effects against both methicillin-resistant S. aureus (MIC: ≤ 16 µg/mL) and glycopeptide-resistant Enterococcus faecium (MIC: ≤ 1 µg/mL). These platanosides were subjected to docking analyses against FabI (enoyl-ACP reductase) and PBP1/2 (penicillin binding protein), both of which are pivotal enzymes governing bacterial growth but not found in the human host. The results showed that 6 and 7 displayed superior binding affinities towards FabI and PBP2. Moreover, surface plasmon resonance studies on the interaction of 1/7 and FabI revealed that 7 has a higher affinity (KD = 1.72 µM), which further supports the above in vitro data and is thus expected to be a novel anti-antibacterial drug lead.

Bioassay-Guided Isolation of New Flavonoid Glycosides from Platanus × acerifolia Leaves and Their Staphylococcus aureus Inhibitory Effects.

Despite the rapid advances in drug R&D, there is still a huge need for antibacterial medications, specifically for the methicillin-resistant Staphylococcus aureus (MRSA). Inspired by the research where a viable class of MRSA inhibitors was found in the species Platanus occidentalis, a S. aureus inhibition screening-guided phytochemical reinvestigation on Platanus × acerifolia (London plane tree) leaves were performed with four flavonoid glycosides garnered, including two new compounds, quercetin-3-O-α-l-(2″-E-p-coumaroyl-3″-Z-p-coumaroyl)-rhamnopyranoside (E,Z-3'-hydroxyplatanoside, 1) and quercetin-3-O-α-l-(2″-Z-p-coumaroyl-3″-E-p-coumaroyl)-rhamnopyranoside (Z,E-3'-hydroxyplatanoside, 2). All of the isolates showed significant S. aureus ATCC 25904 inhibitory activity with MICs ranging from 4 to 64 µg/mL, suggesting the potential of discovering drug leads for the control of S. aureus from such a rich, urban landscaping plant in the Platanus genus.

Phytoconstituent analysis, anti-inflammatory, antimicrobial and anticancer effects of nano encapsulated Convolvulus arvensis L. extracts.

BACKGROUND: The Convolvulus genus is distributed all over the world and has a long history in traditional medicine. As nanotechnology expands its reach into areas like drug delivery and biomedicine, this study intends to assess the potential of Convolvulus arvensis L. extracts as anti-bacterial, anti-inflammatory and anti-cancer agents, along with chemical profiling of the methanolic (MeOH) extract active ingredients. METHODS: The chemical composition of an 85% MeOH extract was investigated by liquid chromatography with an electrospray source connected to mass spectrometry (LC-ESI-MS). Both the 85% MeOH extract and n-butanol fraction of C. arvensis were loaded for the first time on alginate/chitosan nanoparticles. The 85% MeOH extract, n-butanol fraction and their loaded nanoparticles were tested for their cytotoxicity, anticancer, anti-inflammatory and antibacterial activity (against pathogenic bacteria, E. coli and S. aureus). RESULTS: The chemical investigation of 85% MeOH extract of C. arvensis underwent LC-ESI-MS analysis, revealing twenty-six phenolic substances, of which 16 were phenolic acids, 6 were flavonoids, 1 glycolipid, 1 sesquiterpene and 2 unknown compounds. The FT-IR spectra confirmed the encapsulation of the 85% MeOH extract and n-butanol fraction onto alginate/chitosan nanoparticles and small size obtained by TEM maintained them nontoxic and enhanced their anti-inflammatory activity (the IC50 was decreased from 1050 to 175 µg/ml). The anti-cancer activity against HepG2 was increased and the cell viability was decreased from 28.59 ± 0.52 to 20.80 ± 0.27 at a maximum concentration of 1000 µg/ml. In addition, the MIC of encapsulated extracts was decreased from 31.25 to7.78 µg/ml in E. coli (Gm-ve) and from 15.56 to 7.78 µg/ml in S. aureus (Gm + ve) bacteria. CONCLUSION: Both alginate and chitosan are excellent natural polymers for the encapsulation process, which affects positively on the bioactive constituents of C. arvensis extracts and improves their biological properties.

In vitro and in vivo anthelmintic and chemical studies of Cyperus rotundus L. extracts.

BACKGROUND: Trichinellosis, a zoonosis caused by the genus Trichinella, is a widespread foodborne disease. Albendazole, one of the benzimidazole derivatives, is used for treating human trichinellosis, but with limited efficacy in killing the encysted larvae and numerous adverse effects. Cyperus rotundus L. is a herbal plant with a wide range of medicinal uses, including antiparasitic, and is frequently used in traditional medicine to treat various illnesses. METHODS: LC-ESI-MS was used to identify the active phytoconstituents in the methanol extract (MeOH ext.) of the aerial parts of C. rotundus and its derivate fractions ethyl acetate (EtOAc fr.), petroleum ether (pet-ether fr.), and normal butanol (n-BuOH fr.). The in vivo therapeutic effects of C. rotundus fractions of the extracts were evaluated using the fraction that showed the most promising effect after detecting their in vitro anti-Trichinella spiralis potential. RESULTS: C. rotundus extracts are rich in different phytochemicals, and the LC-ESI-MS of the 90% methanol extract identified 26 phenolic compounds classified as phenolic acids, flavonoids, and organic acids. The in vitro studies showed that C. rotundus extracts had a lethal effect on T. spiralis adults, and the LC50 were 156.12 µg/ml, 294.67 µg/ml, 82.09 µg/ml, and 73.16 µg/ml in 90% MeOH ext., EtOAc fr., pet-ether fr. and n-BuOH fr., respectively. The n-BuOH fr. was shown to have the most promising effects in the in vitro studies, which was confirmed by scanning electron microscopy. The in vivo effects of n-BuOH fr. alone and in combination with albendazole using a mouse model were evaluated by counting adults in the small intestine and larvae in the muscles, in addition to the histopathological changes in the small intestine and the muscles. In the treated groups, there was a significant decrease in the number of adults and larvae compared to the control group. Histopathologically, treated groups showed a remarkable improvement in the small intestine and muscle changes. Remarkably, maximal therapeutic effects were detected in the combination therapy compared to each monotherapy. CONCLUSION: Accordingly, C. rotundus extracts may have anti-T. spiralis potential, particularly when combined with albendazole, and they may be used as synergistic to anti-T. spiralis medication therapy.

In vivo evaluation of anticryptosporidial effects of wheat germ extracts in immunocompromised mice.

Cryptosporidium species is a prime cause of diarrheal disease in individuals with competent immunity. In patients with compromised immunity, infections are more severe particularly in developing countries. Wheat germ oil was described to have antiparasitic effect. This study was done to evaluate the possible role of wheat germ extracts in Cryptosporidium parvum (C. parvum) infected immunocompromised mice. Thirty white albino mice were classified into six groups as follow: four study groups, all immunosuppressed and infected with C. parvum oocysts. These four groups received treatments as follow: Group (I): treated with nitazoxanide. Group (II): treated with wheat germ oil. Group (III): treated with wheat germ extracted by hexane. Group (IV): treated with wheat germ extracted by ethanol. The remaining two groups were immunosuppressed control groups as follow: Group (V): only infected with C. parvum oocysts (Positive control). Group (VI): non-infected (Negative control). Stool samples were collected and examined to detect oocyst and the ileocecal region was subjected to histopathological and immunohistochemical examination. Wheat germ extracts showed a statistically significant effect against C. parvum specially wheat germ oil with P value: < 0.001, this effect was also confirmed by pathological and immunohistochemical examinations. C. parvum has an influence on human health by its effect in diarrheal disease. Wheat germ oil and its extracts has proved to be a reliable herb for C. parvum. treatment confirmed by different methodologies.

Phytochemical and biological studies on rare and endangered plants endemic to China. Part XXII. Structurally diverse diterpenoids from the leaves and twigs of the endangered conifer Torreya jackii and their bioactivities.

A phytochemical investigation on the MeOH extract of the leaves and twigs of the endangered conifer Torreya jackii Chun led to the isolation and characterization of 21 structurally diverse diterpenoids. Among them, six are previously undescribed, including four abietane-type (torreyins A-D, resp.) and two labdane-type diterpenoids (torreyins E and F). Their structures and absolute configurations were determined by a combination of spectroscopic methods, calculated/experimental electronic circular dichroism (ECD) data, and single-crystal X-ray diffraction analyses. In particular, torreyins A-C are rare 11,12-seco-abietane type diterpenoids possessing a dilactone moiety, and their biosynthetic pathway starting from a co-occurring abietane derivative (i.e., cyrtophyllone B) was briefly proposed. Among the isolates, 7-oxo-dehydroabietic acid and 15-methoxy-7,13-abietadien-18-oic acid showed considerable inhibitory effects against acetyl-coenzyme A carboxylase 1 (ACC1) and protein tyrosine phosphatase 1 B (PTP1B), with IC50 values of 3.1 and 6.8 µM, respectively.

Phytochemical and biological studies on rare and endangered plants endemic to China. Part XXV. Structurally diverse triterpenoids and diterpenoids from two endangered Pinaceae plants endemic to the Chinese Qinling Mountains and their bioactivities.

A joint phytochemical investigation on the MeOH extracts of the twigs and needles of two endangered Pinaceae plants endemic to the Chinese Qinling Mountains, Picea neoveitchii (an evergreen spruce) and Larix potaninii var. chinensis (a deciduous larch), led to the isolation and characterization of 34 and 24 structurally diverse terpenoids, respectively. Among them, seven are previously undescribed, including a picane-type [i.e., 14(13 â†’ 12)abeo-12αH-serratane] (neoveitchin A) and a serratane-type (neoveitchin B) triterpenoids, and an abietane-type (neoveitchin C) as well as four labdane-type (potalarxins A-D) diterpenoids. Their structures and absolute configurations were established by extensive spectroscopic methods and/or X-ray diffraction analyses. All isolates were evaluated for their inhibitory activities against the human protein tyrosine phosphatase 1B (PTP1B). Serrat-14-en-3α,21ß-diol, betulinic acid, 3ß-hydroxy-11-ursen-13(28)-olide, ursolic acid, and oleanolic acid were found to have considerable inhibitory effects against PTP1B, with IC50 values ranging from 1.1 to 18.1 µM. The interactions of the bioactive triterpenoids with PTP1B were thereafter performed by employing molecular docking studies. In addition, 7-oxo-dehydroabietic acid (an abietane-type diterpenoid) and mangiferonic acid (a cycloartane-type triterpenoid) inhibited acetyl-coenzyme A carboxylase 1 (ACC1), with IC50 values of 3.4 and 6.6 µM, respectively.

Phytochemical and biological studies on rare and endangered plants endemic to China. Part XIV. Structurally diverse terpenoids from the twigs and needles of the endangered plant Picea brachytyla.

A phytochemical investigation on the MeOH extract of the twigs and needles of the endangered plant Picea brachytyla led to the isolation and characterization of thirty-eight structurally diverse terpenoids. Seven of these molecules are previously undescribed, including three abietane-type (brachytylins A-C) and one labdane-type (brachytylin D) diterpenoids, an unseparated C-24 epimeric mixture of cycloartane-type triterpenoids (brachytylins E/F, ratio: 1:1), and a rare rearranged 12(1 → 6)-abeo-megastigmane glycoside (brachytylins G). Their structures and absolute configurations were determined by extensive spectroscopic (e.g., detailed 2D NMR and ECD) methods and/or X-ray diffraction analyses. All the isolates were evaluated for their inhibitory activities against the adenosine triphosphate (ATP)-citrate lyase (ACL) and the Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2). Among them, abiesadine J showed inhibitory effect against ACL, displaying an IC50 value of 17 µM. 3S,23R-Dihydroxycycloart-24-en-26-oic acid exhibited inhibitory effect on SHP2, with an IC50 value of 19 µM. Meanwhile, 3R*,23S*-dihydroxycycloart-24-en-26-oic acid was found to have inhibitory effects against both ACL and SHP2, with IC50 values of 16 and 12 µM, respectively.

Lycofargesiines A-F, further Lycopodium alkaloids from the club moss Huperzia fargesii.

Six undescribed Lycopodium alkaloids (LAs) comprising four lycodine-type (lycofargesiines A-D), one lycopodine-type (lycofargesiine E), and a phlegmarine-type (lycofargesiine F), together with 16 known ones were isolated from the club moss Huperzia fargesii. Their structures and absolute configurations were determined by extensive spectroscopic methods, electronic circular dichroism (ECD) analysis, and density functional theory (DFT) calculations. (7S,8R,12R,13R)-Lycofargesiine A is a rare naturally occurring LA possessing an exocyclic double bond between C-15 and C-16, with ring A being a rare 2,3-dihyropyridone motif. Lycofargesiine D is an uncommon lycodine-type alkaloid featuring a unique N-acetylated tetrahydropyridinyl segment (ring A), whereas lycofargesiine F is the first phlegmarane-type LA bearing two nitrone moieties. In addition to the isolated huperzine A in this study, another two isolates (lycofargesiine C and 16-hydroxyhuperzine A) were also found to show inhibitory activities against acetylcholinesterase (AChE), with IC50 values of 8.63 and 5.18 µM, respectively.

LC-MS guided isolation and dereplication of Lycopodium alkaloids from Lycopodium cernuum var. sikkimense of different geographical origins.

Lycopodium alkaloids (LAs) are the characteristic metabolites of club mosses. Chemical differences often exist in different specimens of a single plant species collected from different geographic origins. In this study, a preliminary LC-MS detection and dereplication analyses of alkaloidal constituents of Lycopodium cernuum var. sikkimense (Müll. Hal.) C.B. Clarke (LCVS2) collected from Fujian province led to the isolation and characterization of three undescribed LAs, lycocernuskines A-C, and six known cernuane-type LAs. The known compounds were previously isolated from the same plant species (LCVS1) collected from Chongqing, and so their dereplication in LCVS2 was accomplished based on their retention times (tR) and the quasi-molecular ion peaks in the LC-MS fingerprint. Chemical structures were identified by spectroscopic methods, single-crystal X-ray diffraction analysis, and electronic circular dichroism calculations. Lycocernuskines A and B are the first two examples of C-12 hydroxylated phlegmarane-type LAs bearing a nitrone residue at the quinoline ring. The isolates were evaluated for their anti-AChE and neuroprotective effects.

LC-MS guided isolation of sinodamines A and B: Chimonanthine-type alkaloids from the endangered ornamental plant Sinocalycanthus chinensis.

Two previously undescribed chimonanthine-type [sinodamines A and B] and five related known dimeric tryptamine-derived alkaloids were isolated and characterized from the leaves of the endangered ornamental plant Sinocalycanthus chinensis under the guidance of LC-MS detection and dereplication analyses, along with conventional isolation procedures. Their structures were established on the basis of spectroscopic methods and chemical transformations. Sinodamine A can be regarded as the naturally occurring N-oxide derivative of its pseudo-mesomer sinodamine B. An acid-catalyzed Meisenheimer rearrangement from sinodamine A to its oxazine-form with a final equilibrium of 1:2 was observed by monitoring their NMR spectra. (-)-Folicanthine showed significant cytotoxicity against human lung carcinoma A549 and colorectal carcinoma HT29 cells, with IC50 values of 7.76 and 6.16 µM, respectively.