ß-acetoxyisovalerylalkannin suppresses proliferation and induces ROS-based mitochondria-mediated apoptosis in human melanoma cells.

ß-acetoxyisovalerylalkannin (ß-AIVA) is one of shikonin/alkannin derivative, which were mainly extracted from Boraginaceae family. The effects of ß-AIVA on human melanoma A375 cells and U918 cells were investigated in vitro. The CCK-8 assay showed that ß-AIVA inhibited proliferation of cells. Results from flow cytometry, ROS assay and JC-1 assay showed that ß-AIVA increased late apoptosis rate, induced the production of ROS and promoted mitochondrial depolarization in cells. ß-AIVA regulated expressions of BAX and Bcl-2 proteins, and increased the expression of cleaved caspase-9 and cleaved caspase-3. These findings suggest that ß-AIVA may be a potential therapeutic drug for treating melanoma.

Progress of studies on natural products for glioblastoma therapy.

Glioblastoma (GBM) is the most common, malignant, and lethal primary brain tumor in adults. Up to now, the chemotherapy approaches for GBM are limited. Therefore, more studies on identifying and exploring new chemotherapy drugs or strategies overcome the GBM are essential. Natural products are an important source of drugs against various human diseases including cancers. With the better understanding of the molecular etiology of GBM, the development of new anti-GBM drugs has been increasing. Here, we summarized recent researches of natural products for the GBM therapy and their potential mechanisms in details, which will provide new ideas for the research on natural products and promote developing drugs from nature products for GBM therapy.

Four new polyprenylated acylphloroglucinol derivatives from Hypericum beanii.

Two new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperbeanins P-Q (1-2), and two new biosynthetic precursors, hyperbeanins R-S (3-4), were isolated from Hypericum beanii, together with three known analogs (5-7). Compound 1 was one of type A PPAPs featured with unusual bicyclo[5.3.1]hendecane core. The structures of isolates were established by NMR spectroscopic methods, experimental electronic circular dichroism (ECD) spectra and comparisons with known compounds. Compounds 5 and 6 showed obvious hepatoprotective activity at 10 µM against paracetamol-induced HepG2 cell damage.

Structural Revision of Hyperibrin B and Hyperscabrones H and I by Biosynthetic Considerations, NMR Analysis, and Chemical Synthesis.

Previously, Gao et al. reported the isolation and structural determination of three natural products, hyperibrin B (HB), hyperscabrone H (HH), and hyperscabrone I (HI), from Hypericum scabrum. HB and HH had different NMR spectroscopic data, but they were assigned identical structures. Furthermore, these compounds should be derived from bicyclic polyprenylated acylphloroglucinols (BPAPs) via degradation, but the assigned structural features of the prenyl and prenylmethyl groups being cis and meta-substituted on the cyclohexanone core were not consistent with their biosynthetic origin. In this note, we revise the structures of HB, HH, and HI via NMR and MS spectroscopic analyses and biosynthetic considerations. We also complete a total synthesis of the revised structure of HB as well as its analogue, hyperibrin A, to further confirm the revision. The revised structures of HB, HH, and HI have not been reported.

Hypseudohenrins I - K: three new polycyclic polyprenylated acylphloroglucinol derivatives from Hypericum pseudohenryi.

Three previously unidentified polycyclic polyprenylated acylphloroglucinols (PPAPs) derivatives, hypseudohenrins I-K (1-3), along with a known analogue hyphenrone X (4), were isolated from the aerial part of Hypericum pseudohenryi. The structures of the new compounds were elucidated by NMR spectroscopy and ECD calculation. The anti-inflammatory activity of the compounds was evaluated. Compounds 1-3 showed mild anti-inflammatory activity while hyphenrone X showed prominent anti-inflammatory activity.[Formula: see text].

Two new polycyclic polyprenylated acylphloroglucinols derivatives from Hypericum acmosepalum.

Polycyclic polyprenylated acylphloroglucinols (PPAPs) were mainly obtained from the plants of Hypericum genus of Guttiferae family, and possessed intriguing chemical structures and appealing biological activities. Two new PPAPs derivatives, hyperacmosin C (1) and hyperacmosin D (2) were isolated from H. acmosepalum. Their structures were established by NMR, HREIMS, and experimental electronic circular dichroism spectra. Besides, compound 1 showed significant hepatoprotective activity at 10 µM against paracetamol-induced HepG2 cell damage and compound 2 could moderately increase the relative glucose consumption.

[Chemical constituents of triterpenoids from Euphorbia resinifera].

The combination of normal-phase silica gel column chromatography, octadecyl silica(ODS) column chromatography, semi-preparative high performance liquid chromatography(HPLC), etc. was employed to isolate and purify the chemical components from Euphorbia resinifera, and 7 triterpenoids were separated from the ethanol extract of the medicinal materials. Their structures were identified by various spectroscopy methods as cycloartan-1,24-diene-3-one(1), cycloartan-1,24-diene-3-ol(2), 3ß-hydroxy-lanosta-8,24-diene-11-one(3), lnonotusane C(4), eupha-8,24-diene-3ß-ol-7,11-dione(5), eupha-24-methylene-8-ene-3ß-ol-7,11-dione(6), and eupha-8,24-diene-3ß,11ß-diol-7-one(7). Compounds 1 and 2 are new compounds, and compound 3 is obtained from nature for the first time.

[Chemical constituents from Hypericum curvisepalum].

This study explored the chemical constituents of the aerial part of Hypericum curvisepalum. Sixteen compounds were isolated from the 95% ethanol extract of H. curvisepalum with various chromatographic techniques, including a new prenylated phenyl polyketide, mysorenone D(1). Other compounds were mysorenone-A(2), mysorenone-C(3), mysorenone-B(4), peplidiforone A(5), 4-methoxy-3-(2-methylbut-3-en-2-yl)-6-phenyl-2H-pyran-2-one(6), hyperenone-A(7), 4-(3,3-dimethylallyl)oxy-6-phenyl-α-pyrone(8), peplidiforone B(9), elegaphenone(10), hypercohin A(11), hyperisampsin G(12), spathulenol(13), quercetin(14), ß-sitosterol(15), and ß-amyrin(16).

Hyperacmosins H-J, three new polycyclic polyprenylated acylphloroglucinol derivatives from Hypericum acmosepalum.

Three new polycyclic polyprenylated acylphloroglucinol derivatives, hyperacmosins H-J (1-3), with four known compounds (4-7), were isolated from the air-dried aerial parts of Hypericum acmosepalum. Especially, compounds 1 and 2 were identified as methylated polycyclic polyprenylated acylphloroglucinol derivatives (mPPAPs). Their structures were established by NMR, HRESIMS and experimental electronic circular dichroism (ECD) spectra. The hepatoprotective activity of seven compounds were evaluated. Compounds 1 and 5 exhibited hepatoprotective activity against paracetamol-induced HepG2 cell damage.[Formula: see text].

Hyperascyrins L - N, rare methylated polycyclic polyprenylated acylphloroglucinol derivatives from Hypericum ascyron.

Seven natural compounds, including new compounds hyperascyrins L-N (1-3) and four known compounds (4-7), were acquired from the aerial parts of Hypericum ascyron, that were all identified as methylated polycyclic polyprenylated acylphloroglucinol derivatives (mPPAPs). The structures of these compounds were established by NMR spectroscopy, experimental and calculated electronic circular dichroism (ECD) data. The neuroprotective activities and hepatoprotective activity of these compounds (10 µM) were evaluated. Compounds 1, 2 and 3 exhibited neuroprotection activity. Compounds 1 and 3 show hepatoprotective activity.

Methylated Polycyclic Polyprenylated Acylphloroglucinol Derivatives from Hypericum ascyron.

Hyperascyrins A-H (1-11) and four known compounds (12-15) were acquired from the air-dried aerial parts of Hypericum ascyron and were all identified as methylated polycyclic polyprenylated acylphloroglucinol derivatives. Their structures were established by NMR spectroscopy, experimental and calculated electronic circular dichroism (ECD) data, and comparison with established compounds. Compounds 8 and 9 showed protection against paracetamol-induced HepG2 cell damage at 10 µM. The neuroprotective activities of all compounds (10 µM) were evaluated, and compounds 1 and 8 exhibited mild neuroprotection against glutamate-induced toxicity in SK-N-SH cells.

Synthesis and antitumor activities of sinomenine derivatives on rings A and C.

A series of new sinomenine derivatives were designed, synthesized, and evaluated in tumor inhibitory activity, such as human triple negative breast cancer cell line (MDA-MB-231), glioma cell line (A172), human lung cancer cell line (A549), human colon cancer cell line (HCT-8). The modifications were carried out on rings A and C of the sinomenine by esterificating on phenolic hydroxyl with good yields. The highlight of this work was that the synthetic procedures were concise and sinomenine derivatives demonstrated promising antitumor activities.

[Chemical constituents of Hypericum perforatum].

A chemical investigation on the aerial parts of Hypericum perforatum resulted in the isolation of a new phloroglucinol derivatives (1), and seven known compounds (2-8). The structures of the compounds were elucidated by means of spectroscopic methods (MS, IR, 1D NMR, and 2D NMR) as 3-methyl-4,6-di (3- methyl-2-butenyl)-3-(4-methyl-3-pentenyl)-2-(2-ethyl-1-oxobutyl)-cyclohexanone (1)，hyperforin (2)，(2R,3R,4S,6R)-3-methyl-4,6-di(3-methyl-2-butenyl)-2-(2-methyl-1-oxo-propyl)-3-(4-methyl-3-pentenyl)-cyclohexanone (3)，hyperscabrin B (4)，hyperscabrin C (5)，furohyperforin isomer 1 (6)，furoadhyperforin (7)，and furohyperforin (8). Compound 1 was a new compound, and compounds 3-5 were obtained from H. perforatum for the first time.

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.

Polycyclic Polyprenylated Acylphloroglucinol Congeners from Hypericum scabrum.

Twenty polycyclic polyprenylated acylphloroglucinols (PPAPs), including the new compounds hyperscabrones A-I (1-9), were isolated from the air-dried aerial parts of Hypericum scabrum. These compounds comprise seven different structural types. All structures were determined by NMR spectroscopic methods and both experimental and calculated electronic circular dichroism (ECD) spectra. The evaluation of their neuroprotective effects on glutamate-induced toxicity in SK-N-SH cells showed that compounds 4-7 exhibited significant neuroprotection at 10 µM. Additionally, compounds 3, 4, 7, and 9 showed moderate hepatoprotective activities against paracetamol-induced HepG2 cell damage at 10 µM.

[Chemical constituents of Myripnois dioica].

To study the chemical constituents of the aerial parts of Myripnois dioica. Twelve compounds were separated from the 95% ethanol extract of M. dioica by using various chromatographic techniques. Their stuctures were identified on the basis of their physicochemical properties and spectral data as 8-desoxyurospermal A(1), zaluzanin C(2), dehydrozaluzanin C(3), glucozaluzanin C(4), macrocliniside B(5), macrocliniside I(6), taraxinic acid-14-O-ß-D-glucopyranoside(7), ainsliaside B(8), apigenin(9), luteolin(10), apigenin-7-O-ß-D-glucopyranoside(11), and luteolin-7-O-ß-D-glucopyranoside(12). Except for compound 8, the other compounds were isolated from this genus for the first time. Compound 8 was found to decrease blood glucose level properly in alloxan-induced diabetic mice.

Effect of Hypericum perforatum L. extract on insulin resistance and lipid metabolic disorder in high-fat-diet induced obese mice.

Natural product Hypericum perforatum L. has been used in folk medicine to improve mental performance. However, the effect of H. perforatum L. on metabolism is still unknown. In order to test whether H. perforatum L. extract (EHP) has an effect on metabolic syndrome, we treated diet induced obese (DIO) C57BL/6J mice with the extract. The chemical characters of EHP were investigated with thin-layer chromatography, ultraviolet, high-performance liquid chromatography (HPLC), and HPLC-mass spectrometry fingerprint analysis. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and the glucose infusion rate (GIR) in hyperinsulinemic-euglycemic clamp test were performed to evaluate the glucose metabolism and insulin sensitivity. Skeletal muscle was examined for lipid metabolism. The results suggest that EHP can significantly improve the glucose and lipid metabolism in DIO mice. In vitro, EHP inhibited the catalytic activity of recombinant human protein tyrosine phosphatase 1B (PTP1B) and reduced the protein and mRNA levels of PTP1B in the skeletal muscle. Moreover, expressions of genes related to fatty acid uptake and oxidation were changed by EHP in the skeletal muscle. These results suggest that EHP may improve insulin resistance and lipid metabolism in DIO mice.

Hepatoprotective benzofurans and furanolignans from Gymnema tingens.

Two new benzofurans, gymnefuranols A (1) and B (2), together with six known furanolignans (3-8), were isolated from Gymnema tingens. The structures of the new compounds were elucidated by comprehensive analysis of the NMR and HR-MS data. Compounds 1, 2, 6, and 7 showed hepatoprotective activities against D-galactosamine-induced HL-7702 cell damage.

Two new oligostilbenes from the stem of Parthenocissus quinquefolia.

Two new oligostilbenes, parthenocissins M (1) and N (2), together with two known compounds, miyabenol C (3) and ϵ-viniferin (4), were isolated from the stem of Parthenocissus quinquefolia. Their structures were elucidated by means of NMR, UV, IR, and MS data.

Two new cucurbitane triterpenoids from the seeds of Momordica charantia.

Two new cucurbitane triterpenoids 1 and 2 were isolated, together with six known compounds, from the seeds of Momordica charantia L. The structures of new compounds were determined to be 3-O-{[ß-d-galactopyranosyl(1 â†’ 6)]-O-ß-d-galactopyranosyl}-23(R), 24(R), 25-trihydroxycucur-bit-5-ene (1), 3-O-[ß-d-galactopyranosyl]-25-O-ß-d-galactopyranosyl-7(R), 22(S), 23(R), 24(R), 25-pentahydroxycucurbit-5-ene (2), respectively. Their structures were elucidated by the combination of mass spectrometry, one- and two-dimensional NMR experiments and chemical reactions.