Initial treatment response and short-term mortality of spontaneous bacterial peritonitis in cirrhotic patients with hepatocellular carcinoma.

This study aimed to investigate the initial treatment response and short-term mortality of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with hepatocellular carcinoma (HCC) compared with those without HCC. A total of 245 patients with liver cirrhosis diagnosed with SBP between January 2004 and December 2020 were included. Of these, 107 (43.7%) were diagnosed with HCC. Overall, the rates of initial treatment failure, 7-day and 30-day mortality were 91 (37.1%), 42 (17.1%), and 89 (36.3%), respectively. While the baseline CTP score, MELD score, culture-positive rate, and rates of antibiotic resistance did not differ between both groups, patients with HCC had a higher rate of initial treatment failure than those without HCC patients (52.3% vs. 25.4%, P < 0.001). Similarly, 30-day mortality was also significantly higher in patients with HCC (53.3% vs. 23.2%, P < 0.001). In the multivariate analysis, HCC, renal impairment, CTP grade C, and antibiotic resistance were independent factors for initial treatment failure. Furthermore, HCC, hepatic encephalopathy, MELD score, and initial treatment failure were independent risk factors for 30-day mortality, with statistically significant poor survival outcomes in patients with HCC (P < 0.001). In conclusion, HCC is an independent risk factor for initial treatment failure and high short-term mortality in patients with cirrhosis with SBP. It has been suggested that more attentive therapeutic strategies are required to improve the prognosis of patients with HCC and SBP.

Assessment of the Aromatase Inhibitory Activity of Ma-Huang-Tang (MHT) and Its Active Compounds.

Aromatase, a cytochrome P450 enzyme that converts androgens into estrogens, is an important drug target for hormone-dependent diseases. The purpose of this study was to elucidate the aromatase inhibitory effects of Ma-Huang-Tang (MHT), a traditional Korean herbal medicine prescription, and to identify its active ingredients. In this study, the inhibitory effect of MHT on aromatase activity was observed using dibenzylfluorescein (DBF) and KGN cells, and the dose-dependent effect of MHT was verified (IC50 values of 251 µg/mL and 246 µg/mL as determined by the two methods, respectively). Furthermore, among the six herbal medicines that constitute MHT, Ephedrae Herba, Cinnamomi Ramulus, and Glycyrrhizae Radix et Rhizoma showed the most potent inhibition of aromatase activity. Furthermore, upon identification of the active MHT compounds, three markers from Glycyrrhizae Radix et Rhizoma, liquiritin (5), liquiritin apioside (6), and liquiritigenin (7), were verified (IC50 values of 530 µM, 508 µM, and 1.611 mM and 499 µM, 522 µM, and 1.41 mM as determined by the two methods, respectively). In addition, their contents were confirmed to be 15.58, 19.80, and 2.22 mg/g, respectively, by HPLC/DAD analysis. These results indicate that the aromatase inhibitory effect of MHT results from the synergistic action of its active components and that MHT has potential as a preventive agent against aromatase activity.

Tetragonia tetragonioides (Pall.) Kuntze Regulates Androgen Production in a Letrozole-Induced Polycystic Ovary Syndrome Model.

Tetragonia tetragonioides (Pall.) Kuntze (TTK) is a medicinal plant traditionally used to treat various diseases such as diabetic, inflammatory, and female-related disorders. Polycystic ovary syndrome (PCOS) is a common endocrinological disorder in women of reproductive age, and hyperandrogenism is a prominent feature of PCOS resulting in anovulation and infertility. In this study, we investigated the effects of a TTK extract on androgen generation and regulation of steroidogenic enzymes in vitro and in vivo. Human adrenocortical NCI-H295R cells were used to assess the effects of TTK extract on production of dehydroepiandrosterone and testosterone, as well as the protein expression of steroidogenic enzymes. Further, a letrozole-induced PCOS rat model was used in vivo to assess whether dietary administration of TTK extract restores normal hormones and reduces PCOS symptoms. TTK extract significantly inhibited forskolin (FOR)-induced androgen production in NCI-H295R cells and serum luteinizing hormone, testosterone, and follicular cysts, but not estradiol, were reduced in letrozole-induced PCOS rats orally administered the TTK extract. In addition, TTK extract inhibits androgen biosynthesis through the ERK-CREB signaling pathway, which regulates CYP17A1 or HSD3B2 expression. TTK extract could be utilized for the prevention and treatment of hyperandrogenism and other types of PCOS.

Lignans from the stems and leaves of Brandisia hancei and their effects on VEGF-induced vascular permeability and migration of HRECs and DLAV formation in zebrafish.

In our continuing search for novel antiangiogenic agents, a new lignan glycoside, (7R,8R)-1-(4-O-ß-d-glucopyranosyl-3-methoxyphenyl)-2-{2-methoxy-4-[1-(E)-propene-3-ol]-phenoxyl}-propane-1,3-diol (1), along with three known lignans (2-4), were isolated from the 80% EtOH extract of Brandisia hancei stems and leaves. These isolates (1-4) were subjected to an in vitro bioassay to evaluate their effects on vascular endothelial growth factor (VEGF)-induced vascular permeability and migration of human retinal endothelial cells (HRECs). Of the compounds tested, compound 1 resulted in the greatest reduction in VEGF-induced vascular permeability by about 31.5% at 10 µM compared to the VEGF-treated control. In the migration assay, compounds 1 and 2 significantly decreased VEGF-induced HREC migration. Furthermore, zebrafish embryos treated with compounds 1 and 2 showed mild reductions of dorsal longitudinal anastomotic vessel (DLAV) formation.

Caffeoylated phenylpropanoid glycosides from Brandisia hancei inhibit advanced glycation end product formation and aldose reductase in vitro and vessel dilation in larval zebrafish in vivo.

In our continuing efforts to identify effective naturally sourced agents for diabetic complications, five caffeoylated phenylpropanoid glycosides, acteoside (1), isoacteoside (2), poliumoside (3), brandioside (4), and pheliposide (5) were isolated from the 80% EtOH extract of Brandisia hancei stems and leaves. These isolates (1-5) were subjected to an in vitro bioassay evaluating their inhibitory activity on advanced glycation end product formation and rat lens aldose reductase activity. All tested compounds exhibited significant inhibition of advanced glycation end product formation with IC50 values of 4.6-25.7 µM, compared with those of aminoguanidine (IC50=1,056 µM) and quercetin (IC50=28.4 µM) as positive controls. In the rat lens aldose reductase assay, acteoside, isoacteoside, and poliumoside exhibited greater inhibitory effects on rat lens aldose reductase with IC50 values of 0.83, 0.83, and 0.85 µM, respectively, than those of the positive controls, 3,3-tetramethyleneglutaric acid (IC50=4.03 µM) and quercetin (IC50=7.2 µM). In addition, the effect of acteoside on the dilation of hyaloid-retinal vessels induced by high glucose in larval zebrafish was investigated. Acteoside reduced the diameters of high glucose-induced hyaloid-retinal vessels by 69% at 10 µM and 81% at 20 µM, compared to the high glucose-treated control group. These results suggest that B. hancei and its active components might be beneficial in the treatment and prevention of diabetic vascular complications.

Effects of Allium victorialis leaf extracts and its single compounds on aldose reductase, advanced glycation end products and TGF-ß1 expression in mesangial cells.

BACKGROUND: Accumulating evidences suggest that aldose reductase (AR) inhibitors and advanced glycation end product (AGE) formation inhibitors may prevent chronic hyperglycemia-induced long-term complication in diabetes. Transforming growth factor-beta1 (TGF-ß1) plays an important role in the development of diabetic nephropathy. Allium species have been utilized in folk medicine throughout the world for the treatment of various physical disorders. However, the benefits of Allium victorialis (A. victorialis) against diabetic complications, especially nephropathy, have yet to be explored. In the present study, we investigated the protective effect of the compounds isolated from A. victorialis leaf on diabetic nephropathy. METHODS: In vitro AR activity, AGEs formation, and AGE-receptor for AGEs (RAGE) binding in human RAGE (hRAGE)-overexpressing cells were tested. High glucose-induced transforming growth factor-beta1 (TGF-ß1) expression was also examined in mouse kidney mesangial cells (MMCs) cultured under high glucose. RESULTS: Of the isolated eight compounds from A. victorialis leaf extracts tested, quercitrin exhibited the most pronounced inhibitory effects on AR activity (IC50 value of 0.17 µM) and AGEs formation (IC50 value of 4.20 µM). Furthermore, quercitrin disrupted AGE-RAGE binding in a concentration-dependent manner in hRAGE-overexpressing cells. Additionally, of the eight compounds tested, ferulic acid significantly reduced high glucose-induced TGF-ß1 expression and secretion in MMCs. CONCLUSIONS: Our results suggest that active compounds isolated from A. victorialis leaf exhibit inhibitory effects on AR activity in rat lenses and AGE formation. Further, ferulic acid reduces TGF-ß1 mRNA expression and secretion in MMCs under diabetic conditions. Thus, A. victorialis is a good candidate for the development of treatments for diabetic nephropathy.

Proanthocyanidins from Spenceria ramalana and their effects on AGE formation in vitro and hyaloid-retinal vessel dilation in larval zebrafish in vivo.

Three new A-type proanthocyanidins (1-3), ent-epiafzelechin-(2α→O→7,4α→8)-ent-afzelechin 3'-O-ß-D-glycopyranoside (1), ent-epiafzelechin-(2α→O→7,4α→8)-ent-epiafzelechin-(2α→O→7,4α→8)-ent-afzelechin (2), and ent-epiafzelechin-(2α→O→7,4α→8)-ent-epicatechin-(2α→O→7,4α→8)-ent-afzelechin (3), and three known compounds (4-6) were isolated from the whole plant of Spenceria ramalana. The structures of the new proanthocyanidins were established by spectroscopic and chemical studies. The inhibitory effects of compounds 1-6 on the formation of advanced glycation end products were examined in vitro. Compounds 3 and 6 showed the strongest inhibition, with IC50 values of 17.4 ± 0.5 and 14.1 ± 1.6 µM, respectively. The effects of these isolates on the dilation of hyaloid-retinal vessels induced by high glucose (HG) in larval zebrafish were also investigated. Compound 3 reduced the dilation of HG-induced hyaloid-retinal vessels most effectively. This compound reduced the diameters of HG-induced hyaloid-retinal vessels by about 157.7% and 164.1% at 10 and 20 µM, respectively, versus the HG-treated control group.