IL-6 Inhibitory Compounds from the Aerial Parts of Piper attenuatum and Their Anticancer Activities on Ovarian Cancer Cell Lines.

Piper attenuatum Buch-Ham, a perennial woody vine belonging to the Piperaceae family, is traditionally used in Southeast Asia for treating various ailments such as malaria, headache, and hepatitis. This study described the isolation and identification of three new compounds, piperamides I-III (1-3), which belong to the maleimide-type alkaloid skeletons, along with fifteen known compounds (4-18) from the methanol extract of the aerial parts of P. attnuatum. Their chemical structures were elucidated using spectroscopic methods (UV, IR, ESI-Q-TOF-MS, and 1D/2D NMR). All the isolates were evaluated for their ability to inhibit IL-6 activity in the human embryonic kidney-Blue™ IL-6 cell line and their cytotoxic activity against ovarian cancer cell lines (SKOV3/SKOV3-TR) and chemotherapy-resistant variants (cisplatin-resistant A2780/paclitaxel-resistant SKOV3). The compounds 3, 4, 11, 12, 17, and 18 exhibited IL-6 inhibition comparable to that of the positive control bazedoxifene. Notably, compound 12 displayed the most potent anticancer effect against all the tested cancer cell lines. These findings highlight the importance of researching the diverse activities of both known and newly discovered natural products to fully unlock their potential therapeutic benefits.

Dipterocarpus tuberculatus Roxb. Ethanol Extract Has Anti-Inflammatory and Hepatoprotective Effects In Vitro and In Vivo by Targeting the IRAK1/AP-1 Pathway.

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1ß in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.

Begonia myanmarica (Begoniaceae), a new species from Myanmar, and molecular phylogenetics of Begonia sect. Monopteron.

BACKGROUND: A new species, Begonia myanmarica, was discovered from Myanmar and herein documented. Characterized by a single developed wing in the ovary/fruit, this species would be assigned to sect. Monopteron (sensu Doorenbos et al. in The sections of Begonia including descriptions, keys and species lists: studies in Begoniaceae VI. Wageningen Agricultural University, Wageningen, 1998) that is known by B. griffithiana and B. nepalensis from the Himalaya. To confirm its sectional assignment, we conducted morphological, phylogenetic and cytological studies. RESULTS: Morphological observations indicated that B. myanmarica was distinguishable from the two known species of sect. Monopteron by the leaf shape and size, 1-locular ovary, parietal placentation and chromosome number. Molecular phylogenetic analysis using nrITS sequences showed that B. myanmarica was not allied with the clade of sect. Monopteron, though both were nested within sect. Platycentrum-sect. Sphenanthera clade. CONCLUSIONS: Studies of morphology, molecular phylogenetics and cytology support the recognition of the new species, Begonia myanmarica, which is fully described and illustrated. Our results also indicate that B. myanmarica is not closely related to species previously assigned to sect. Monopteron, suggesting that the fruit morphology of a single developed wing in the ovary/fruit characterizing sect. Monopteron is homoplasious.

Flavonoid glycosides from the aerial parts of Acacia pennata in Myanmar.

Phytochemical investigations of the aerial parts of Acacia pennata (Mimosaceae) from Myanmar led to the isolation of five flavonoid glycosides and six known compounds. The new compounds were identified as (2R,3S)-3,5,7-trihdyroxyflavan-3-O-α-L-rhamnopyranoside, (2S)-5,7-dihydroxyflavan-7-O-ß-D-glucopyranoside-(4α → 8)-epiafzelechin-3-O-gallate, (2R)-4',7-dihydroxyflavan-(4α → 8)-(2R,3S)-3,5,7-trihdyroxyflavan-3″-O-α-L-rhamnopyranoside, 5,7-dihydroxyflavone 6-C-ß-boivinopyranosyl-7-O-ß-D-glucopyranoside, and 5,7-dihydroxyflavone 7-O-ß-D-glucopyranosyl-8-C-ß-boivinopyranoside based on interpretation of spectroscopic data.

Two new phenolic glucosides from Lagerstroemia speciosa.

Two new phenolic glucosides, 1-O-benzyl-6-O-E-caffeoyl-ß-d-glucopyranoside and 1-O-(7S,8R)-guaiacylglycerol-(6-O-E-caffeoyl)-ß-d-glucopyranoside, were isolated from the aerial parts of Lagerstroemia speciosa, along with ten known compounds. The structures of the isolated compounds were determined based on 1D- and 2D-NMR, Q-TOF MS and optical rotation spectroscopic data. All of the compounds showed moderate inhibitory activities against nitric oxide production in lipopolysaccharide-treated RAW264.7 cells, with IC50 values of 69.5-83.3 µM.

Flavonoids from Symplocos racemosa.

A novel isoflavone glycoside, peseudobatigenin 7-O-[ß-d-apiofuranosyl-(1''''→5''')-O-ß-d-apiofuranosyl-(1'''→6'')]-ß-d-glucopyranoside, namely sympracemoside (1), was isolated from the aerial parts of Symplocos racemosa along with 15 known flavonoids (2-16). Their structures were characterized by Q-TOF mass, optical rotation, UV, 1D and 2D-NMR spectroscopic data. Compounds 3, 9, 16 showed moderate inhibitory activities against NO production with IC50 value of 88.2, 42.1 and 74.3 µM, respectively.

Syk/Src-targeted anti-inflammatory activity of Codariocalyx motorius ethanolic extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Codariocalyx motorius (Houtt.) H. Ohashi (Fabaceae) is one of several ethnopharmacologically valuable South Asian species prescribed as an herbal medicine for various inflammatory diseases. Due to the lack of systematic studies on this plant, we aimed to explore the inhibitory activity of Codariocalyx motorius toward inflammatory responses using its ethanolic extract (Cm-EE). MATERIALS AND METHODS: Lipopolysaccharide (LPS)-treated macrophages and a HCl/EtOH-induced gastritis model were used for evaluation of the anti-inflammatory activity of Cm-EE. HPLC and spectroscopic analysis were employed to identify potential active components. Mechanistic approaches to determine target enzymes included kinase assays, reporter gene assays, and overexpression of target enzymes. RESULTS: Cm-EE strongly suppressed nitric oxide (NO) and prostaglandin E2 (PGE2) release. Cm-EE-mediated inhibition was observed at the transcriptional level in the form of suppression of NF-κB (p65) translocation and activation. This extract also lowered the levels of phosphorylation of Src and Syk, their kinase activity, and their formation of signalling complexes by binding to the downstream enzyme p85/PI3K. In accord with these findings, the phosphorylation of p85 induced by overexpression of Src or Syk was also diminished by Cm-EE. Orally administered Cm-EE clearly inhibited gastritic ulcer formation and the phosphorylation of IκBα and Src in HCl/EtOH-treated stomachs of mice. By phytochemical analysis, luteolin and its glycoside, apigenin-7-O-glucuronide, and scutellarein-6-O-glucuronide were identified as major components of Cm-EE. Among these, it was found that luteolin was able to strongly suppress NO and PGE2 production under the same conditions. CONCLUSION: Syk/Src-targeted inhibition of NF-κB by Cm-EE could be a major anti-inflammatory mechanism contributing to its ethno pharmacological role as an anti-inflammatory herbal medicine.

Myrsine seguinii ethanolic extract and its active component quercetin inhibit macrophage activation and peritonitis induced by LPS by targeting to Syk/Src/IRAK-1.

ETHNOPHARMACOLOGICAL RELEVANCE: Myrsine seguinii H. LÉVEILLÉ (syn. Rapanea neriifolia) (Myrsinaceae) is a medicinal plants traditionally used in Myanmar to treat infectious and inflammatory diseases. Since none of reports have systematically demonstrated the anti-inflammatory activity of this plant, we aimed to mechanistically understand the regulatory roles of the plant in inflammatory responses using the ethanolic extract of Myrsine seguinii (Ms-EE). MATERIALS AND METHODS: Activated macrophages and peritonitis symptoms induced by lipopolysaccharide (LPS) were employed. HPLC analysis was used to identify active components. To characterize direct target enzymes, kinase assay was established. RESULTS: Ms-EE inhibited the production of nitric oxide (NO) and prostaglandin (PG)E2 in RAW264.7 cells and peritoneal macrophages stimulated by LPS. This extract suppressed the mRNA expression of the inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 genes by down-regulating the activation of nuclear factor (NF)-κB and activator protein (AP-1). Interestingly, it was found that Ms-EE can directly suppress the enzyme activities of Syk, Src, and interleukin-1 receptor-associated kinase-1 (IRAK-1). Similarly, orally administered Ms-EE inhibited the phosphorylation of Src and Syk in peritoneal exudate-derived cells prepared from peritonitis. Finally, HPLC analysis clearly demonstrated that quercetin is a major active component with suppressing activity on the release of inflammatory mediators (NO and PGE2), and the enzyme activities of Src, Syk, and IRAK-1. CONCLUSION: Ms-EE containing quercetin negatively modulates macrophage-mediated in vitro inflammatory responses and LPS-induced peritonitis by blocking the Src/Syk/NF-κB and IRAK-1/AP-1 pathways, which contributes to its major ethnopharmacological use as an anti-inflammatory herbal medicine.

Dipterocarpus tuberculatus ethanol extract strongly suppresses in vitro macrophage-mediated inflammatory responses and in vivo acute gastritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Dipterocarpus tuberculatus Roxb. (Dipterocarpaceae) has been traditionally used to treat various inflammatory symptoms. However, no mechanistic studies on the anti-inflammatory actions of D. tuberculatus have been reported. This study is therefore aimed at exploring the anti-inflammatory effects of 95% ethanol extracts (Dt-EE) of this plant. MATERIALS AND METHODS: The regulatory activity of Dt-EE and its molecular mechanism on the release of nitric oxide (NO) and prostaglandin (PG)E2 in lipopolysaccharide (LPS)-treated macrophage-like RAW264.7 cells were elucidated by evaluating the activation of transcription factors and their upstream signals and by analyzing the kinase activities of target enzymes. Furthermore, to confirm its availability for oral use, an EtOH/HCl-induced acute gastritis model was tested with this extract. RESULTS: Dt-EE effectively suppressed LPS-mediated inflammatory responses such as the production of NO and PGE2 from macrophages in a dose-dependent manner. In particular, Dt-EE clearly blocked the activation of NF-κB by blocking the phosphorylation of its upstream enzymes IKK and Akt. Using a direct enzyme assay, Dt-EE was shown to block the enzyme activity of PDK1. Finally, this extract also remarkably ameliorated inflammatory lesions in the stomach induced by EtOH/HCl. CONCLUSION: Our data strongly suggest that Dt-EE can be considered as a novel anti-inflammatory remedy with PDK1/NF-κB inhibitory properties and can also be used to treat gastritis symptoms. In addition, our findings can serve as a basis for further phytochemical and pharmacological studies in the future.