Qinge Ma

Hepatoprotective phenylethanoid glycosides from Cirsium setosum

Abstract Two new phenylethanoid glycosides, namely β-D-glucopyranoside, 1″-O-(7S)-7-(3-methoxyl-4-hydroxyphenyl)-7-methoxyethyl-3″-α-L-rhamnopyranosyl-4″-[(8E)-7-(3-methoxyl-4-hydroxyphenyl)-8-propenoate] (1) and β-D-glucopyranoside, 1″-O-(7S)-7-(3-methoxyl-4-hydroxyphenyl)-7-methoxyethyl-3″-α-L-rhamnopyranosyl-4″-[(8E)-7-(4-hydroxyphenyl)-8-propenoate] (2), together with six phenylethanoid glycosides were isolated from Cirsium setosum. Their structures were elucidated by their spectroscopic data and references. Compounds 2, 4, 5, 7 and 8 (10 μM) exhibited moderate hepatoprotective activities. Compounds (3–8) were obtained from this plant for the first time.

Design, synthesis and evaluation of novel ferulic acid-memoquin hybrids as potential multifunctional agents for the treatment of Alzheimer’s disease

A novel series of ferulic acid-memoquin hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimers disease (AD). The in vitro studies showed that most of the compounds exhibited a significant ability to inhibit acetylcholinesterase (AChE) (IC50 of 3.2-34.7μM) and self-induced β-amyloid (Aβ1-42) aggregation (30.8-39.1%, 25μM), to act as potential antioxidants (ORAC-FL value of 0.9-1.3). In particular, compound 17d had the greatest ability to inhibit AChE (IC50=3.2μM), and Aβ1-42 aggregation (30.8%) was also an excellent antioxidant and neuroprotectant. Moreover, it is capable of disaggregating self-induced Aβ aggregation. Furthermore, 17d could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 17d is a potential multifunctional agent for the treatment of AD.

Alkenes with antioxidative activities from Murraya koenigii (L.) Spreng.

Four new alkenes (1-4), and six known alkenes (5-12) were isolated from Murraya koenigii (L.) Spreng. Their structures were elucidated on the basis of spectroscopic analyses and references. Compounds (1-12) were evaluated for antioxidative activities. Among them, compounds 1, 2, 4, and 7 exhibited significant antioxidative activities using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay with IC50=21.4-49.5 μM. The known compounds (5-12) were isolated from this plant for the first time.

Design, synthesis and biological evaluation of 3,4-dihydro-2(1H)-quinoline-O-alkylamine derivatives as new multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer’s disease

A new family of multitarget molecules able to interact with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as with monoamino oxidase (MAO) A and B, has been synthesized. Novel 3,4-dihydro-2(1H)-quinoline-O-alkylamine derivatives have been designed using a conjunctive approach that combines the JMC49 and donepezil. The most promising compound TM-33 showed potent and balance inhibitory activities toward ChE and MAO (eeAChE, eqBuChE, hMAO-A and hMAO-B with IC50 values of 0.56μM, 2.3μM, 0.3μM and 1.4μM, respectively) but low selectivity. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that TM-33 binds simultaneously to the catalytic active site and peripheral anionic site of AChE. Furthermore, our investigation proved that TM-33 could cross the blood-brain barrier (BBB) in vitro, and abided by Lipinskis rule of five. The results suggest that compound TM-33, an interesting multi-targeted active molecule, offers an attractive starting point for further lead optimization in the drug-discovery process against Alzheimers disease.

Bioactive alkaloids from the aerial parts of Houttuynia cordata

ETHNOPHARMACOLOGICAL RELEVANCE Houttuynia cordata is an important traditional Chinese medicine used in heat-clearing and detoxifying, swelling and discharging pus, promoting diuresis and relieving stranguria which recorded in Pharmacopoeia of the peoples Republic of China (2015 Edition). H. cordata has been recorded in the book Bencaogangmu which was written by Shizhen Li for the treatment of pyretic toxicity, carbuncle swelling, haemorrhoids, and rectocele diseases. AIM OF THE STUDY Phytochemical investigation of the aerial parts of H. cordata and evaluation of their PTP1B inhibitory activities and hepatoprotective activities. MATERIALS AND METHODS The dried aerial parts of H. cordata were fractionated by liquid-liquid extraction to obtain CHCl3, ethyl acetate, and n-butanolic fractions. The CHCl3 fraction was confirmed active fraction by the bioactivity-guided investigation, which was isolated and purified by chromatographing over silica gel, Sephadex LH-20, MPLC, and preparative HPLC. The chemical structures of the purified compounds were identified by their spectroscopic data and references. RESULTS Eight new compounds (1-8), together with fourteen known compounds (9-22) were isolated from the aerial parts of H. cordata. The known compounds (9-22) were obtained from this plant for the first time. Among them, some compounds exhibited moderate bioactivities. CONCLUSION Compounds (1-8) were identified as new alkaloids, and the known alkaloids (9-22) were isolated from this plant for the first time. Compounds 1, 4, 14, and 19 showed significant PTP1B inhibitory activities with IC50 values of 1.254, 2.016, 2.672, and 1.862µm, respectively. Compounds 1, 3, 6, 11, 17, and 20 (10µm) exhibited moderate hepatoprotective activities against D-galactosamine-induced WB-F344 cells damage.

Phenylethanoid Glycosides from Houttuynia cordata and Their Hepatoprotective Activities

Houttuynia cordata Thunb., belonging to the Saururacea family, is well known by the name “Yu-Xing-Cao.” It is widely distributed in China and has been used as a plant medicine for relieving fever, promoting urination, and reducing swelling in folk [1]. Modern pharmacology has shown that H. cordata has antiviral, anti-inflammatory, and immunostimulating activities [2]. Previous phytochemical investigations of H. cordata showed the presence of flavonoids [3], alkaloids [4], organic acids, and essential oils [5]. To the best of our knowledge, there have been no reports on the hepatoprotective activities of H. cordata, which prompted us to further investigate its pharmacological potentials. As a result, 13 compounds (1–13) were isolated and identified as phenylethanoid glycosides on the basis of extensive spectroscopic analysis. These compounds were identified by their MS and NMR spectra, and all the data were in good agreement with those reported in the references. General. NMR spectra (1H NMR, 13C NMR) were recorded on Bruker-400, with TMS as internal standard. The ESI-MS data were acquired on an Agilent 1100 series LC/MSD Trap SL mass spectrometer. Column chromatography was run on Sephadex LH-20 (Amersham Pharmacia, Sweden) and silica gel H, 100–200 mesh and 200–300 mesh (Qingdao Marine Chemical Inc., Qingdao, China). TLC was performed on precoated silica gel GF254 plates, and the spots were visualized under UV light (254 or 356 nm) or by spraying with 10% H2SO4 in 95% EtOH followed by heating [15]. Plant Material. H. cordata was harvested from Nanyang, Henan Province, China, in August 2013. A voucher specimen (No. NNU201308) has been deposited in Nanyang Normal University. Extraction and Isolation. The whole air-dried and powdered plant of H. cordata (6.0 kg) was extracted three times with 95% EtOH (8 L 3) and heating under reflux to give 700 g of crude extract. The combined extracts were successively partitioned with petroleum ether, EtOAc, and n-BuOH to yield three fractions: petroleum ether soluble fraction (85.0 g), EtOAc soluble fraction (128.5 g), and n-butanol soluble fraction (245.0 g). The n-butanol soluble fraction was subjected to column purification with macroporous adsorbent resin (Diaion-101) and eluted with 15%, 30%, 50%, and 95% ethanol to obtain four fractions: A (35.5 g), B (64.0 g), C (42.8 g), and D (17.4 g). The B part was purified on a Sephadex LH-20 column with a gradient system of MeOH–H2O to give three subfractions: B-a, B-b, B-c. Repeated separation of B-a (8.80 g) by silica gel (100–200 mesh or 200–300 mesh) yielded 8 (11.00 mg), 5 (8.50 mg), 7 (10.50 mg), and 10 (9.60 mg). The B-b part was repeatedly chromatographed over Sephadex LH-20 and silica gel successively to yield 12 (7.60 mg), 13 (12.50 mg), 3 (13.10 mg), and 4 (9.10 mg). Similarly, the C part was chromatographed over Sephadex LH-20 and silica gel and eluted with different mobile phases, yielding 6 (14.00 mg), 9 (16.00 mg), 11 (9.30 mg), 1 (13.80 mg), and 2 (9.70 mg). Plantainoside A (1). C23H26O11, white powder. 1H NMR (400 MHz, CD3OD, , ppm, J/Hz): 6.69 (1H, d, J = 2.0, H-2), 6.66 (1H, d, J = 8.0, H-5), 6.54 (1H, dd, J = 8.0, 2.0, H-6), 3.90 (1H, m, H), 3.74 (1H, m, H), 2.79 (2H, t, J = 7.0, H), 4.44 (1H, d, J = 8.0, H-1 ), 5.05 (1H, d, J = 9.0, H-3 ), 7.08 (1H, d, J = 2.0, H-2 ), 6.80 (1H, d, J = 8.0, H-5 ), 6.97 (1H, dd, J = 8.0, 2.0, H-6 ), 7.58 (1H, d, J = 16.0, H-7 ), 6.33 (1H, d, J = 16.0, H-8 ) [6].

Cytotoxic Anthraquinones from the Aerial Parts of Acalypha australis

Acalypha australis L., belonging to the Euphorbiaceae family, is used in folk medicine to threat diarrhea, hematemesis, uterine bleeding, dermatitis, and as an expectorant [1]. It is widely distributed in farmlands and roadsides throughout southern China [2]. Previous phytochemical investigations of A. australis showed the presence of terpenoids and anthraquinones [3], organic acids and saccharides [4], flavonoids, and tannins [5]. Modern pharmacology revealed that A. australis had a variety of pharmacological activities, such as antibacterial [6], antioxidant [7], hemostatic [8], and antiulcerative [9] activities. After consulting a large number of references, we found that there were few reports on the cytotoxic activities of A. australis, which prompted us to further study its pharmacological potentials. We carried out a bioassay-guided investigation of A. australis in order to evaluate its bioactivities. As a result, 14 compounds were isolated from the active fractions (EtOAc fraction) of A. australis, which were identified as anthraquinones on the basis of their extensive spectroscopic analysis. All the compounds (1–14) were obtained from this plant for the first time. It is important that compounds 5, 9, 10, 12, and 14 exhibited moderate cytotoxicities against a small panel of human tumor cell lines with IC50 values in the range of 5.24–15.37 M. General Procedures. UV spectra were measured with the Australia GBC UV-916 spectrophotometer, NMR data were recorded on an Bruker-400 spectrometer with TMS as internal standard. IR spectra were measured with a Nicolet 5700 FT-IR microscope spectrometer. ESI-MS data were measured using a Q-Trap LC/MS/MS (TurbolinSpray source) spectrometer. Reversed-phase HPLC was performed using an Agilent 1200 series chromatograph with a DIKMA (4.6 250 mm) analytical column packed with C18 (5 m). Column chromatography was carried out on Sephadex LH-20 (Amersham Pharmacia, Sweden) and silica gel H, 160–200 mesh and 200–300 mesh (Qingdao Marine Chemical Inc., Qingdao, China). TLC was performed on precoated silica gel GF254 plates, and the spots were visualized under UV light (254 or 365 nm) or by spraying with 10% H2SO4 in 95% EtOH followed by heating. Plant Material. The aerial parts of A. australis were harvested from Nanyang, Henan Province, China, in September 2013. A voucher specimen (No. NNUTXC-201309) has been deposited in Nanyang Normal University. Extraction and Isolation. The dried aerial parts of A. australis (8.0 kg) were extracted with 95% EtOH (10 L 3) three times, each time for 3 h. After removal of the solvent under reduced pressure, the residue (0.9 kg) was suspended in H2O and partitioned successively with petroleum ether, ethyl acetate, and n-butanol [10] to obtain three fractions: petroleum ether soluble fraction (93.0 g), EtOAc soluble fraction (220.6 g), and n-butanol soluble fraction (288.0 g). According to the bioassayguided investigation of A. australis, we found that the EtOAc soluble fraction showed potential cytotoxic activity. Therefore, the EtOAc soluble fraction was subjected to a silica gel column chromatography (CC) and eluted with petroleum ether– acetone (10:1–1:5) to obtain four fractions: A (36.5 g), B (86.5 g), C (44.8 g), and D (22.5 g). Fraction B was chromatographed on a silica gel column and eluted with petroleum ether–acetone (8:1–1:1) to give three subfractions B-a–B-c. The separation of B-a (12.60 g) by silica gel (100–200 mesh or 200–300 mesh) and Sephadex LH-20, repeatedly, yielded 2 (9.60 mg), 7 (11.20 mg), 9 (12.20 mg), 10 (10.60 mg), and 13 (15.00 mg).

Carbazole alkaloids with antiangiogenic activities from Clausena sanki

Two new carbazole alkaloids 1 and 2, and eleven known congeners 3-13 were isolated and identified from Clausena sanki for the first time. Their structures were elucidated on the basis of extensive UV, IR, MS, NMR spectroscopic data and comparison with literatures. The compounds 1-13 were evaluated by MTT assay to determine whether they decreased VEGF-mediated cell proliferation in HUVECs with Axitinib as positive control. Among them, compounds 1, 2, 6, 8, and 13 (μM) exhibited moderate antiangiogenic activities, which inhibited VEGF-induced HUVEC proliferation in vitro with IC50 values of 12.1 (C.I. 8.2-15.2), 58.1 (C.I. 56.3-63.4), 13.7 (C.I. 9.2-15.4), 16.0 (C.I. 9.5-16.4), and 63.2 (C.I. 57.8-65.7) μM, respectively. Moreover, the antiangiogenic activities of compounds 1-13 were evidenced in vivo in the zebrafish embryo model. As a result, compounds 1, 2, 6, 8, and 13 showed effectively suppress angiogenesis. These research results may guide the search for new natural products with antiangiogenic attributes.