Two new monoterpene esters from the pericarps of Alpinia zerumbet.

Two new monoterpene esters (1 and 2) and four known compounds (3-6) were isolated from the pericarps of Alpinia zerumbet. Their structures were elucidated by extensive spectroscopic analyses and their anti-inflammatory activity was evaluated by monitoring their inhibitory effects on the interleukin-1ß-induced production of nitric oxide in primary cultured rat hepatocytes. The new compound 1 and cardamonin 3 showed inhibitory activities with IC50 values of 17.6 ± 1.1 and 10.2 ± 1.3 µM, respectively, which are comparable to that of the positive control NG-methyl-L-arginine acetate salt.

Correction to: Antiinflammatory constituents of Atractylodes chinensis rhizome improve glomerular lesions in immunoglobulin A nephropathy model mice.

The article Antiinflammatory constituents of Atractylodes chinensis rhizome improve glomerular lesions in immunoglobulin A nephropathy model mice, written by Toshinari Ishii, Tetsuya Okuyama, Nao Noguchi, Yuto Nishidono, Tadayoshi Okumura, Masaki Kaibori, Ken Tanaka, Susumu Terabayashi, Yukinobu Ikeya and Mikio Nishizawa was originally published Online First without Open Access. After publication in volume 74 issue 1, page 51-64 the author decided to opt for Open Choice and to make the article an Open Access publication. Therefore, the copyright of the article has been changed to © The Author(s) 2020 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Antiinflammatory constituents of Atractylodes chinensis rhizome improve glomerular lesions in immunoglobulin A nephropathy model mice.

The crude drug Sojutsu, as defined by the Japanese Pharmacopoeia, is the rhizome of Atractylodes lancea De Candolle, Atractylodes chinensis Koidzumi, or their interspecific hybrids (Asteraceae). Sojutsu is one of the traditional Kampo formulas, which are administered to patients suffering from stomach disorders, edema, and nephrotic syndrome. Although antiinflammatory effects of Sojutsu have been reported, its effects on the liver and kidney have not been extensively investigated. Here, we used a Sojutsu sample identified as A. chinensis rhizome and isolated several constituents from its ethyl acetate (EtOAc)-soluble fraction that decreased production of the proinflammatory mediator nitric oxide (NO) in interleukin 1ß-treated rat hepatocytes. Among the constituents in this fraction, atractylodin showed the highest activity to suppress NO production, whereas hinesol, ß-eudesmol, and α-bisabolol showed low activity. Atractylodin decreased the levels of inducible nitric oxide synthase, tumor necrosis factor α, and lipocalin 2 messenger RNAs (mRNAs). The EtOAc-soluble fraction of the A. chinensis rhizome extract was administered daily for 20 weeks to high immunoglobulin A (HIGA) mice, whose pathological findings resemble human immunoglobulin A nephropathy. This fraction decreased the weight of white adipose tissue and decreased mesangial proliferation and immunoglobulin A deposition in glomeruli. These results indicate that the EtOAc-soluble fraction, which included antiinflammatory constituents, may be responsible for improvement of the mesangial lesions in HIGA mice.

Bitter melon fruit extract has a hypoglycemic effect and reduces hepatic lipid accumulation in ob/ob mice.

Bitter melon (Momordica charantia L.) is a vegetable and has been used as traditional medicine. Recently, we reported that bitter melon fruit extracts and its ethyl acetate (EtOAc)-soluble fraction markedly suppressed the expression of proinflammatory genes, including the inducible nitric oxide synthase gene. However, it is unclear whether bitter melon exhibits antidiabetic effects. In this study, we showed that cucurbitacin B, a cucurbitane-type triterpenoid, was present in an EtOAc-soluble fraction and suppressed nitric oxide production in hepatocytes. When the EtOAc-soluble fraction was administered for 7 days to ob/ob mice, a type 2 diabetes mellitus model, the mice fed with this fraction exhibited a significant decrease in body weight and blood glucose concentrations compared with the mice fed without the fraction. The administration of the fraction resulted in significant increases in serum insulin concentrations and the levels of both insulin receptor mRNA and protein in the ob/ob mouse liver. The EtOAc-soluble fraction decreased the interleukin-1ß mRNA expression, as well as hepatic lipid accumulation in hepatocytes. Taken together, these results indicate that administration of an EtOAc-soluble fraction improved hyperglycemia and hepatic steatosis, suggesting that this fraction may be responsible for both the antidiabetic and anti-inflammatory effects of bitter melon fruit.

Effect of heat processing on the chemical constituents and NO-suppressing activity of Bletilla Tuber.

Bletilla Tuber (dried tuber of Bletilla striata) is used as an astringent hemostatic medicine for the treatment of ulcers, bleeding, and burns in traditional Chinese medicine (TCM). The Chinese Pharmacopoeia describes the heat processing methods used on raw tubers of Bletilla striata to produce the herbal medicine "Bletilla Tuber". In this study, we compared the chemical constituents of well-processed Bletilla Tuber (BT1) and normally processed Bletilla Tuber (BT2) derived from the same origin. In addition, as an indicator of the hemostatic activity of Bletilla Tuber, the NO inhibitory activities of extracts obtained from BT1 and BT2 and the isolated compounds were examined. As a result of LC-MS analysis, three types of compounds, glucosyloxybenzyl 2-isobutylmalates, bibenzyl derivatives and phenanthrene derivatives, were detected. Comparison of the chemical profiles of the extracts indicated that the relative contents of glucosyloxybenzyl 2-isobutylmalates had changed by heat processing, whereas the relative contents of bibenzyls and phenanthrenes had not changed. The extracts of BT1 and BT2 showed similar IC50 values on NO production suppressing activity. Furthermore, phenanthrenes and bibenzyls were identified as the compounds responsible for suppressing the NO activity. These results suggest that the biological activities, such as the anti-inflammatory and hemostatic activities, of Bletilla Tuber are not affected by heat processing.

Sakuranetin downregulates inducible nitric oxide synthase expression by affecting interleukin-1 receptor and CCAAT/enhancer-binding protein ß.

Pruni Cortex is a herbal drug from the bark of the Japanese flowering cherries, Prunus jamasakura or Prunus verecunda, and is included in the traditional Japanese herbal (Kampo) formula Jumihaidokuto, which is administered orally to patients suffering from inflammatory skin diseases. The flavanones contained in Pruni Cortex (e.g., sakuranetin and naringenin) have potent anti-inflammatory, anti-allergic, and anti-microbial activities. Although the effects of Pruni Cortex on skin disease have been well studied, reports regarding its pharmacological effects on the liver are limited. In this study, we extracted the bark of Prunus jamasakura and purified it to isolate the pharmacologically active constituents by monitoring nitric oxide (NO) production in rat hepatocytes that were treated with the pro-inflammatory cytokine, interleukin (IL)-1ß. Sakuranetin and (-)-naringenin, which were present in an ethyl acetate-soluble fraction of the bark extract, significantly inhibited NO induction and inducible nitric oxide synthase (iNOS) expression. These two flavanones decreased the expression of type 1 IL-1 receptor gene and phosphorylation of Akt, also known as protein kinase B, which is regulated by phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K). Furthermore, sakuranetin decreased the phosphorylation of the activator isoforms of CCAAT/enhancer-binding protein ß (C/EBPß), which synergistically activates the transcription of the iNOS gene with nuclear factor κB (NF-κB). Therefore, sakuranetin inhibited the co-activating activity of C/EBPß with NF-κB, leading to the suppression of iNOS gene expression in hepatocytes. Taken together, sakuranetin in Pruni Cortex downregulated the iNOS gene by inhibiting PI3K/Akt signal transduction and the phosphorylation of C/EBPß. These results imply that sakuranetin may be primarily responsible for the anti-inflammatory effects of Pruni Cortex in the liver.