Two aromatic acid derivatives and a xanthone from <i>Hypericum hengshanense</i>

Three previously undescribed compounds including two aromatic acid derivatives (1–2), and one xanthone (3), together with ten known compounds (4–13) were isolated from the aerial part of Hypericum hengshanense. The planar structures of three new compounds were established by 1 D and 2 D NMR and MS data. And the absolute configurations of compounds 1–2 were determined by the quantum chemical ECD calculations. Compounds 1–2 showed weak cytotoxicity against Hep-2 human cancer cell lines with IC50 values of 65.1 ± 2.7 and 78.0 ± 1.0 μg/mL, respectively.</p

Isoliensinine, a Bioactive Alkaloid Derived from Embryos of <i>Nelumbo nucifera</i>, Induces Hepatocellular Carcinoma Cell Apoptosis through Suppression of NF-κB Signaling

Isoliensinine (isolie) is an alkaloid produced by the edible plant <i>Nelumbo nucifera</i>. Here, we unveiled that isolie was able to provoke HepG2, Huh-7, and H22 hepatocellular carcinoma (HCC) cell apoptosis. Isolie decreased NF-κB activity and constitutive phosphorylation of NF-κB p65 subunit at Ser536 in HCC cells. Overexpression of p65 Ser536 phosphorylation mimics abrogated isolie-mediated HCC cell apoptosis. Furthermore, intraperitoneal injection of isolie inhibited the growth of Huh-7 xenografts in nude mice. Additionally, isolie given by both intraperitoneal injection and gavage diminished the proliferation of transplanted H22 cells in Kunming mice. Reduced tumor growth in vivo was associated with inhibited p65 phosphorylation at Ser536 and declined NF-κB activity in tumor tissues. Finally, we revealed that isolie was bioavailable in the blood of mice and exhibited no detectable toxic effects on tumor-bearing mice. Our data provided strong evidence for the anti-HCC effect of isolie

Image_3_Essential Oil Derived From Eupatorium adenophorum Spreng. Mediates Anticancer Effect by Inhibiting STAT3 and AKT Activation to Induce Apoptosis in Hepatocellular Carcinoma.jpg

<p>Eupatorium adenophorum Spreng. (EA) is a well-known noxious invasive species. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that the essential oil derived from EA (EAEO) is mainly composed of sesquiterpenes. However, the pharmacological value of EAEO in hepatocellular carcinoma (HCC) remains largely unexplored. Herein, we investigated the anti-HCC activities of EAEO, and explored the potential mechanisms of EAEO-induced apoptosis. An MTT assay showed that EAEO inhibited HCC cell proliferation with little toxicity on normal liver cells. Wound healing and FACS assays revealed that EAEO suppressed HCC cell migration and arrested cell cycle, respectively. Moreover, EAEO promoted in vitro HCC cell apoptosis, and EAEO treatment inhibited HepG2 xenografts growth and enhanced apoptotic nucleus of xenografts in HepG2-bearing nude mice. Mechanistically, EAEO significantly decreased the ratio of Bcl-2/Bax and resulted in the activation of caspase-9 and -3. EAEO also reduced the expression of Grp78, which in turn relieved the inhibition of caspase-12 and -7. Meanwhile, EAEO suppressed the phosphorylation of STAT3 and AKT, indicative of its anti-HCC potential. In summary, we determined that EAEO treatment promoted HCC apoptosis via activation of the apoptotic signaling pathway in mitochondria and endoplasmic reticulum, as well as repressed the activity of STAT3 and AKT in HCC cells.</p

Two new megastigmanes from Chinese traditional medicinal plant <i>Sedum sarmentosum</i>

<p>To discover new bioactive compounds from nature plants, a primary screening of traditional Chinese medicines had been taken. The screening results showed that a EtOAc extract of <i>Sedum sarmentosum</i> displayed a certain degree of cytotoxic activity and bioassay-directed isolation of EtOAc extract gave two new megastigmanes, <i>(6S,9R)</i>-2-hydroxy-4-(2,6,6-trimethyl-4-oxo-cyclohex-2-enyl)-butyric acid (<b>1</b>) and <i>(6S,9R)</i>-2-hydroxy-4-(2,6,6-trimethyl-4-oxo-cyclohex-2-enyl)-butyric acid methyl ester (<b>2</b>) together with seven known flavonoids. The chemical structures of <b>1</b> and <b>2</b> were elucidated on the basis of detailed 1D, 2D NMR and MS data. When tested against HepG2 and Hep3B hepatocellular carcinoma cell lines, compounds <b>1</b>–<b>9</b> showed weak anti-HCC activity. In addition, <i>in vitro</i> antioxidant activities of <b>1</b>–<b>9</b> were evaluated by ABTS radical cation-scavenging assay. <b>1</b> and <b>2</b> exhibited weak activity with per micromoles equivalent to 0.039 and 0.042 μM of Trolox, respectively. The flavonoid component, quercetin (<b>9</b>) showed the highest antioxidant activities with per micromoles equivalent 0.67 μM of Trolox.</p

Evaluation of anti-nociceptive and anti-inflammatory activities of the methanol extract of Holigarna caustica (Dennst.) Oken leaves

Ethnopharmacological relevance: Holigarna caustica (Dennst.) is commonly used in traditional medicine to treat a variety of painful conditions such as eye irritation, inflammation, arthritis, skin diseases, cuts and wounds.Aim of the study: The present study was undertaken to investigate the anti-nociceptive and anti-inflammatory activities of the methanol extract of H. caustica leaves and to elucidate its possible mechanism(s) of action.Materials and methods: Fresh leaves of H. caustica were collected, dried, and extracted with methanol (MEHC). MEHC was subjected to activity testing, using chemical-induced (acetic acid and formalin test) and heat-induced (hot plate and tail immersion test) pain models. To determine the possible mechanism behind the anti-nociceptive activity of MEHC, the opioid antagonist naltrexone was used to evaluate the involvement of opioid receptors in the case of formalin, hot plate and tail immersion tests, while the involvement of the cGMP and ATP-sensitive K+ channel pathways were assessed using methylene blue and glibenclamide respectively, in the acetic acid-induced writhing test. In parallel, the carrageenan-induced paw oedema model was used to determine the anti-inflammatory potential of the extract. Exploratory and motor behaviours were evaluated by the open-field test. Various bioactive compounds potentially responsible for the anti-nociceptive and anti-inflammatory activities were ascertained using GC-MS analysis.Results: MEHC showed strong, significant and dose-dependent anti-nociceptive activity in all chemical-induced and heat-induced pain models at all experimental doses. The association of opioid receptors with the observed anti-nociceptive effects was confirmed by using naltrexone. The cGMP and ATP-sensitive K+ channel pathway was also shown to be involved in the anti-nociceptive activity of MEHC. In addition, MEHC exhibited a dose-dependent inhibition of inflammatory oedema induced by carrageenan. MEHC was not connected with changes in either the locomotor activity or motor responses of mice. In a GC-MS analysis, 40 compounds were identified, among which twelve are documented bioactive compounds with potent analgesic and anti-inflammatory properties.Conclusions: Our current study revealed that MEHC possesses strong central and peripheral anti-nociceptive as well as anti-inflammatory activity. It may also be concluded that both opioid receptors as well as the cGMP and ATP-sensitive K+ channel pathway are involved in the anti-nociceptive mechanism of MEHC. This study rationalizes the ethnomedicinal use of H. caustica leaves in various painful conditions.</p

Data_sheet_1_Essential Oil Derived From Eupatorium adenophorum Spreng. Mediates Anticancer Effect by Inhibiting STAT3 and AKT Activation to Induce Apoptosis in Hepatocellular Carcinoma.DOCX

<p>Eupatorium adenophorum Spreng. (EA) is a well-known noxious invasive species. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that the essential oil derived from EA (EAEO) is mainly composed of sesquiterpenes. However, the pharmacological value of EAEO in hepatocellular carcinoma (HCC) remains largely unexplored. Herein, we investigated the anti-HCC activities of EAEO, and explored the potential mechanisms of EAEO-induced apoptosis. An MTT assay showed that EAEO inhibited HCC cell proliferation with little toxicity on normal liver cells. Wound healing and FACS assays revealed that EAEO suppressed HCC cell migration and arrested cell cycle, respectively. Moreover, EAEO promoted in vitro HCC cell apoptosis, and EAEO treatment inhibited HepG2 xenografts growth and enhanced apoptotic nucleus of xenografts in HepG2-bearing nude mice. Mechanistically, EAEO significantly decreased the ratio of Bcl-2/Bax and resulted in the activation of caspase-9 and -3. EAEO also reduced the expression of Grp78, which in turn relieved the inhibition of caspase-12 and -7. Meanwhile, EAEO suppressed the phosphorylation of STAT3 and AKT, indicative of its anti-HCC potential. In summary, we determined that EAEO treatment promoted HCC apoptosis via activation of the apoptotic signaling pathway in mitochondria and endoplasmic reticulum, as well as repressed the activity of STAT3 and AKT in HCC cells.</p

Image_2_Essential Oil Derived From Eupatorium adenophorum Spreng. Mediates Anticancer Effect by Inhibiting STAT3 and AKT Activation to Induce Apoptosis in Hepatocellular Carcinoma.jpg

<p>Eupatorium adenophorum Spreng. (EA) is a well-known noxious invasive species. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that the essential oil derived from EA (EAEO) is mainly composed of sesquiterpenes. However, the pharmacological value of EAEO in hepatocellular carcinoma (HCC) remains largely unexplored. Herein, we investigated the anti-HCC activities of EAEO, and explored the potential mechanisms of EAEO-induced apoptosis. An MTT assay showed that EAEO inhibited HCC cell proliferation with little toxicity on normal liver cells. Wound healing and FACS assays revealed that EAEO suppressed HCC cell migration and arrested cell cycle, respectively. Moreover, EAEO promoted in vitro HCC cell apoptosis, and EAEO treatment inhibited HepG2 xenografts growth and enhanced apoptotic nucleus of xenografts in HepG2-bearing nude mice. Mechanistically, EAEO significantly decreased the ratio of Bcl-2/Bax and resulted in the activation of caspase-9 and -3. EAEO also reduced the expression of Grp78, which in turn relieved the inhibition of caspase-12 and -7. Meanwhile, EAEO suppressed the phosphorylation of STAT3 and AKT, indicative of its anti-HCC potential. In summary, we determined that EAEO treatment promoted HCC apoptosis via activation of the apoptotic signaling pathway in mitochondria and endoplasmic reticulum, as well as repressed the activity of STAT3 and AKT in HCC cells.</p

Image_1_Essential Oil Derived From Eupatorium adenophorum Spreng. Mediates Anticancer Effect by Inhibiting STAT3 and AKT Activation to Induce Apoptosis in Hepatocellular Carcinoma.jpg

<p>Eupatorium adenophorum Spreng. (EA) is a well-known noxious invasive species. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that the essential oil derived from EA (EAEO) is mainly composed of sesquiterpenes. However, the pharmacological value of EAEO in hepatocellular carcinoma (HCC) remains largely unexplored. Herein, we investigated the anti-HCC activities of EAEO, and explored the potential mechanisms of EAEO-induced apoptosis. An MTT assay showed that EAEO inhibited HCC cell proliferation with little toxicity on normal liver cells. Wound healing and FACS assays revealed that EAEO suppressed HCC cell migration and arrested cell cycle, respectively. Moreover, EAEO promoted in vitro HCC cell apoptosis, and EAEO treatment inhibited HepG2 xenografts growth and enhanced apoptotic nucleus of xenografts in HepG2-bearing nude mice. Mechanistically, EAEO significantly decreased the ratio of Bcl-2/Bax and resulted in the activation of caspase-9 and -3. EAEO also reduced the expression of Grp78, which in turn relieved the inhibition of caspase-12 and -7. Meanwhile, EAEO suppressed the phosphorylation of STAT3 and AKT, indicative of its anti-HCC potential. In summary, we determined that EAEO treatment promoted HCC apoptosis via activation of the apoptotic signaling pathway in mitochondria and endoplasmic reticulum, as well as repressed the activity of STAT3 and AKT in HCC cells.</p

Chemical composition and antimicrobial activity of Congea tomentosa, an ethnomedicinal plant from Bangladesh.

Congea tomentosa Roxb. (CT) is used as a medicinal plant by indigenous peoples of Bangladesh, but to date remains largely unexplored from a phytochemical or pharmacological perspective. In this study, the extracts of leaves, stems and flowers of CT were tested for antimicrobial activity using the agar well diffusion and micro-dilution methods. Compared with leaf and flower extracts, the crude stem extract was the most effective against the tested microorganisms. Therefore, the crude stem extract was further subjected to sequential fractionation, with the petroleum ether and ethyl acetate extracts proving the most active against tested microorganisms. Using GC–MS analysis, 10 compounds were identified within the petroleum ether extract, all of which are known to the literature, and some/all of which may have contributed to the observed antimicrobial properties. Additionally, two compounds (β-amyrin and stigmasterol) were isolated from the ethyl acetate fraction and identified using mass spectrometry and NMR spectroscopy. Compound 2 (stigmasterol) displayed promising antimicrobial activity against tested microorganisms. Despite the ethnobotanical importance of CT, this work represents the first scientific report supporting its traditional use, and demonstrates that both the stem extract of this ethnomedicinal plant and the isolated compound 2 (stigmasterol) may offer potential as antimicrobials

Presentation_1_Antidiabetic Activity of a Flavonoid-Rich Extract From Sophora davidii (Franch.) Skeels in KK-Ay Mice via Activation of AMP-Activated Protein Kinase.pdf

<p>The present study was undertaken to investigate the hypoglycemic activity and potential mechanisms of action of a flavonoid-rich extract from Sophora davidii (Franch.) Skeels (SD-FRE) through in vitro and in vivo studies. Four main flavonoids of SD-FRE namely apigenin, maackiain, leachianone A and leachianone B were purified and identified. In vitro, SD-FRE significantly promoted the translocation and expression of glucose transporter 4 (GLUT4) in L6 cells, which was significantly inhibited by Compound C (AMPK inhibitor), but not by Wortmannin (PI3K inhibitor) or Gö6983 (PKC inhibitor). These results indicated that SD-FRE enhanced GLUT4 expression and translocation to the plasma membrane via the AMPK pathway and finally resulted in an increase of glucose uptake. In vivo, using a spontaneously type 2 diabetic model, KK-Ay mice received intragastric administration of SD-FRE for 4 weeks. As a consequence, SD-FRE significantly alleviated the hyperglycemia, glucose intolerance, insulin resistance and hyperlipidemia in these mice. Hepatic steatosis, islet hypertrophy and larger adipocyte size were observed in KK-Ay mice. However, these pathological changes were effectively relieved by SD-FRE treatment. SD-FRE promoted GLUT4 expression and activated AMPK phosphorylation in insulin target tissues (muscle, adipose tissue and liver) of KK-Ay mice, thus facilitating glucose utilization to ameliorate insulin resistance. Regulation of ACC phosphorylation and PPARγ were also involved in the antidiabetic effects of SD-FRE. Taken together, these findings indicated that SD-FRE has the potential to alleviate type 2 diabetes.</p