Antiangiogenic activity of terpenoids from Euphorbia neriifolia Linn.

Angiogenesis is known to serve an important role in embryonic development, wound healing, tissue regeneration, and growth. Two new abietane-type diterpenoids (3, 5), a new lanosterol triterpenoid (8) and seven known compounds haven been isolated from the Euphorbia neriifolia Linn. The structures of all compounds were elucidated by spectroscopic analysis and comparing their NMR data with reported data. Furthermore, we found that compounds 6 and 9 had the antiangiogenic effects in vitro. They could inhibit HUVEC migration and microvessel sprouting in rat aortic rings. Moreover, compound 6 inhibited VEGFR and phosphorylation of Akt, but compound 9 only shown inhibitory effect on phosphorylation of Akt. Taken together, these results suggest that inhibition of VEGF signaling and downstream pathways may be responsible for the antiangiogenic activity of compounds 6 and 9.

The wound healing potential of collagen peptides derived from the jellyfish Rhopilema esculentum.

PURPOSE: Wound represents a major health challenge as they consume a large amount of healthcare resources to improve patient's quality of life. Many scientific studies have been conducted in search of ideal biomaterials with wound-healing activity for clinical use and collagen has been proven to be a suitable candidate biomaterial. This study intended to investigate the wound healing activity of collagen peptides derived from jellyfish following oral administration. METHODS: In this study, collagen was extracted from the jellyfish--Rhopilema esculentum using 1% pepsin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fourier transform infrared (FTIR) were used to identify and determine the molecular weight of the jellyfish collagen. Collagenase II, papain and alkaline proteinase were used to breakdown jellyfish collagen into collagen peptides. Wound scratch assay (in vitro) was done to determine migration potential of human umbilical vein endothelial cells (HUVEC) covering the artificial wound created on the cell monolayer following treatment with collagen peptides. In vivo studies were conducted to determine the effects of collagen peptides on wound healing by examining wound contraction, re-epithelialization, tissue regeneration and collagen deposition on the wounded skin of mice. Confidence level (p < 0.05) was considered significant using GraphPad Prism software. RESULTS: The yield of collagen was 4.31%. The SDS-PAGE and FTIR showed that extracted collagen from jellyfish was type I. Enzymatic hydrolysis of this collagen using collagenase II produced collagen peptides (CP1) and hydrolysis with alkaline proteinase/papain resulted into collagen peptides (CP2). Tricine SDS-PAGE revealed that collagen peptides consisted of protein fragments with molecular weight <25 kDa. Wound scratch assay showed that there were significant effects on the scratch closure on cells treated with collagen peptides at a concentration of 6.25 µg/mL for 48 h as compared to the vehicle treated cells. Overall treatment with collagen peptide on mice with full thickness excised wounds had a positive result in wound contraction as compared with the control. Histological assessment of peptides treated mice models showed remarkable sign of re-epithelialization, tissue regeneration and increased collagen deposition. Immunohistochemistry of the skin sections showed a significant increase in ß-fibroblast growth factor (ß-FGF) and the transforming growth factor-ß1 (TGF-ß1) expression on collagen peptides treated group. CONCLUSION: Collagen peptides derived from the jellyfish-Rhopilema esculentum can accelerate the wound healing process thus could be a therapeutic potential product that may be beneficial in wound clinics in the future.

Quorumolides A-C, Three Cembranoids from Euphorbia antiquorum.

Three highly modified cembranoids, quorumolides A-C (1-3), were isolated from Euphorbia antiquorum. Compound 1 is the first example of a cembranoid embedding an α,ß-unsaturated-γ-lactone and a tetrahydro-2H-pyran motif within the 14-membered ring. Biosynthetically, it is particularly noteworthy that the stereochemistries of C-2 and C-12 in the pyran ring of 1-3 were opposite to those of marine-derived rare cembranoids.

A New 1,5-Dihydroxy-4-methoxyisoquinoline from Scolopendra subspinipes mutilans.

A new isoquinoline, 1,5-dihydroxy-4-methoxyisoquinoline (1), was obtained from Scolopendra subspinipes mutilans. Compound 1 showed moderate cytotoxicity on tumour cells with IC50 values ranging from 13 to 26 µm against five esophageal squamous cancer cells whereas low cytotoxicity against normal human esophageal epithelial cells. Isoquinoline ring oxidized at C(1), C(4), and C(5) can enhance its cytotoxicity. In addition, compound 1 showed potent inhibitory effect (inhibition rate > 50% at 13 µm) on cell migration in human umbilical vein endothelial cells. This article mainly studies the structure and activity of 1, and more modification of 1 as a potential anticancer agent.

Ingol-type diterpenes from Euphorbia antiquorum with mouse 11ß-hydroxysteroid dehydrogenase type 1 inhibition activity.

Eighteen new ingol-type diterpenes, euphorantins A-R (1-18), along with four known analogues (19-22), were isolated from the aerial parts of Euphorbia antiquorum. Compounds 1-3 are the first examples of C-17-oxygenated ingol-type diterpenes, and compounds 16-18 represent a rare class of 2,3-di-epimers of ingols. Diterpenes 1, 14, and 22 exhibited inhibitory activities against mouse 11ß-HSD1 with IC50 values of 12.0, 6.4, and 0.41 µM, respectively.

Eurifoloids A-R, structurally diverse diterpenoids from Euphorbia neriifolia.

Eighteen new diterpenoids, named eurifoloids A-R (1-18), including ingenane (1 and 2), abietane (3-7), isopimarane (8-12), and ent-atisane (13-18) types, along with four known analogues were isolated from Euphorbia neriifolia. Eurifoloid M (13) represents a rare class of ent-atisane-type norditerpenoid. Eurifoloids E (5) and F (6) exhibited significant anti-HIV activities, with EC50 values of 3.58 ± 0.31 (SI = 8.6) and 7.40 ± 0.94 µM (SI = 10.3), respectively.

Centranthera grandiflore alleviates alcohol-induced oxidative stress and cell apoptosis.

Alcohol liver disease (ALD) has become a global threat to human health. It is associated with a wide range of liver diseases including alcohol fatty liver, steatosis, fibrosis and cirrhosis, and finally leads to liver cancer and even death. Centranthera grandiflora is a traditional Chinese medicinal herb commonly used to treat ALD, but no research about its mechanism is available. This study evaluated the hepatoprotective effect and mechanism of C. grandiflora against alcohol-induced liver injury in mice. We found that the ethanol extracts of C. grandiflora (CgW) alleviated the alcohol-induced liver injury, enhanced the levels of antioxidant enzymes, and reduced the amount of lipid peroxides. CgW also affected cell apoptosis by inhibiting the activity of Bax, cleaved-caspase 3 and cleaved-caspase 9, and increasing the activity of Bcl-2. In conclusion, the results showed that CgW can effectively improve ALD through alleviating oxidative stress and inhibiting cell apoptosis for the first time. This study suggested that C. grandiflora is a promising herbal medicine for ALD treatment.

Antifungal activities of triterpenoids from the roots of Astilbe myriantha Diels.

During a search for plant extracts that possess activity against the fungi that cause diseases in plants, a 95% ethanol extract from the roots of Astilbe myriantha Diels showed inhibitory activity against Colletotrichum gloeosporioides. Bioassay-guided fractionation of the 95% ethanol extract led to the isolation of seven triterpenoids (1-7). Their structures were elucidated by spectroscopy and by a comparison with literature data. Among these compounds, 3ß,6ß,24-trihydroxyurs-12-en-27-oic acid (7) was the most active inhibitor of C. gloeosporioides, with >68.0% inhibition at 100mg/ml after 72h. Moreover, compound 7 displayed broad-spectrum inhibitory activity against Rhizoctonia solani, Fusarium oxysporum f. sp. Niveum, Fusarium oxysporum f. sp. Cubens, C. gloeosporioides, Penicillium citrinum, Colletotrichum lagenarium, and Penicillium digitatum, with EC50 values ranging from 13.9 to 34.0µg/ml. The potential of compound 7 as a fungicide is therefore promising. In addition, compound 1 was found to be a new triterpenoid, 3ß,6ß-dihydroxyurs-12-en-7α,27α-olide, which possesses six rings.

Deheiculatins A-L, 20-oxygenated cembranoids from Macaranga deheiculata.

Twelve cembranoids, deheiculatins A-L, were isolated from the leaves and twigs of Macaranga deheiculata. Their structures were elucidated on the basis of spectroscopic data. Five of these compounds displayed moderate inhibitory activity against human and/or mouse 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1). 20-Oxygenated cembranes are rare.

New arbutin derivatives from the leaves of Heliciopsis lobata with cytotoxicity.

Heliciopsis lobata is a medicinal plant, which is exclusively used to treat tumor in Li folk region. Two new arbutin derivatives, 6'-((E)2-methoxy-5-hydroxycinnamoyl) arbutin (1) and 2'-((E)2, 5-dihydroxycinnamoyl) arbutin (2) along with five known compounds (3-7), were isolated from the leaves of Heliciopsis lobata. Their structures were elucidated on the basis of extensive spectroscopic interpretations. They were evaluated for their potential anticancer activity. Compounds 6 and 7 exhibited cytotoxicity against MGC-803 cells with IC50 values being 44.1 and 11.3 µg·mL-1, respectively. Additionally, compounds 1, 2 and 5-7 exhibited a moderate inhibition of MGC-803 cells invasion; compound 2 at 20 µg·mL-1 inhibited the invasion of MGC-803 cells by 43.0%, compared with the controls.

Two new isoquinoline alkaloids from Scolopendra subspinipes mutilans induce cell cycle arrest and apoptosis in human glioma cancer U87 cells.

Two new isoquinoline alkaloids 1-2 and seven known compounds 3-9 were isolated from the ethanol extract of centipede Scolopendra subspinipes mutilans L. Koch. The structures were elucidated by a combination of spectroscopic analyses including 1D and 2D NMR, and HRESIMS. Compounds 1-2 exhibited good cytotoxicity with IC50 values ranging from 1.19 to 31.28µM against six human cancer cell lines and low cytotoxicity against human normal liver L-02 cell lines, suggesting that compounds 1-2 had high specific cytotoxicity on human cancer cell lines. Further analyses showed that compounds 1-2 inhibited U87 cells proliferation by arresting cell cycle progress at G0/G1 phase and inducing apoptosis through loss of mitochondrial membrane potential (MMP), activation of caspase 9/3 and down-regulation of the Bcl-2/Bax protein ratio. The results suggest that compounds 1-2 induce apoptosis in U87 cells through the mitochondria apoptosis pathway, and they deserve further research as potential anti-glioma cancer agents.

Cytotoxicity and structure activity relationships of phytosterol from Phyllanthus emblica.

Fourteen sterols (1-14), including two new sterols, trihydroxysitosterol (2) and 5α,6ß,7α-7α-acetoxysitosterol (3), were isolated from the branches and leaves of Phyllanthus emblica L. The isolated compounds and a structurally related sterol 15 from Aphanamixis grandifolia were screened for cytotoxicity in two tumor cell lines (HL-60 and SMMC-7721) and a non-tumor cell line (HL-7702) using RSB assay. Within the series of phytosterol derivatives tested, compound 15 was the most active, displaying potent cytotoxicity against HL-60 with IC(50) of 5.10µmol/L, and most of the active compounds showed selective cytotoxicity against tumor and non-tumor cell lines, especially compound 10 with a safety index of 4.42.

Highly oxygenated stigmastane-type steroids from the aerial parts of Vernonia anthelmintica Willd.

Nine new highly oxygenated stigmastane-type steroids, vernoanthelcin A-I (1-9), and two new stigmastane-type steroidal glycosides, vernoantheloside A and B (10 and 11) were isolated from the aerial parts of Vernonia anthelmintica Willd. The structures of compounds 1-11 were determined on the basis of IR, MS, 1D-NMR, and 2D-NMR, and their absolute configurations were deduced using single-crystal X-ray diffraction and the CD exciton chirality method. Compounds 1, 5, 7, 9 and 10 were tested for their effects on estrogen biosynthesis in human ovarian granulosa-like cells (KGN cells).