Panaxcerol D from Panax ginseng ameliorates the memory impairment induced by cholinergic blockade or Aß25-35 peptide in mice.

Background: Alzheimer's disease (AD) has memory impairment associated with aggregation of amyloid plaques and neurofibrillary tangles in the brain. Although anti-amyloid ß (Aß) protein antibody and chemical drugs can be prescribed in the clinic, they show adverse effects or low effectiveness. Therefore, the development of a new drug is necessarily needed. We focused on the cognitive function of Panax ginseng and tried to find active ingredient(s). We isolated panaxcerol D, a kind of glycosyl glyceride, from the non-saponin fraction of P. ginseng extract. Methods: We explored effects of acute or sub-chronic administration of panaxcerol D on cognitive function in scopolamine- or Aß25-35 peptide-treated mice measured by several behavioral tests. After behavioral tests, we tried to unveil the underlying mechanism of panaxcerol D on its cognitive function by Western blotting. Results: We found that pananxcerol D reversed short-term, long-term and object recognition memory impairments. The decreased extracellular signal-regulated kinases (ERK) or Ca2+/calmodulin-dependent protein kinase II (CaMKII) in scopolamine-treated mice was normalized by acute administration of panaxcerol D. Glial fibrillary acidic protein (GFAP), caspase 3, NF-kB p65, synaptophysin and brain-derived neurotrophic factor (BDNF) expression levels in Aß25-35 peptide-treated mice were modulated by sub-chronic administration of panaxcerol D. Conclusion: Pananxcerol D could improve memory impairments caused by cholinergic blockade or Aß accumulation through increased phosphorylation level of ERK or its anti-inflammatory effect. Thus, panaxcerol D as one of non-saponin compounds could be used as an active ingredient of P. ginseng for improving cognitive function.

Dysregulated Liver Metabolism and Polycystic Ovarian Syndrome.

A significant fraction of couples around the world suffer from polycystic ovarian syndrome (PCOS), a disease defined by the characteristics of enhanced androgen synthesis in ovarian theca cells, hyperandrogenemia, and ovarian dysfunction in women. Most of the clinically observable symptoms and altered blood biomarker levels in the patients indicate metabolic dysregulation and adaptive changes as the key underlying mechanisms. Since the liver is the metabolic hub of the body and is involved in steroid-hormonal detoxification, pathological changes in the liver may contribute to female endocrine disruption, potentially through the liver-to-ovary axis. Of particular interest are hyperglycemic challenges and the consequent changes in liver-secretory protein(s) and insulin sensitivity affecting the maturation of ovarian follicles, potentially leading to female infertility. The purpose of this review is to provide insight into emerging metabolic mechanisms underlying PCOS as the primary culprit, which promote its incidence and aggravation. Additionally, this review aims to summarize medications and new potential therapeutic approaches for the disease.

Inhibitory effect of ginsenglactone A from Panax ginseng on the tube formation of human umbilical vein endothelial cells and migration of human ovarian cancer cells.

Background: Here, we aimed to assess the inhibitory effect of a new compound from Panax ginseng on the migration of human ovarian cancer cells and tube formation of human umbilical vein endothelial cells (HUVECs). Methods: A new compound, ginsenglactone A (1), was isolated from ginseng roots, together with seven known compounds (2-8). Spectroscopic data were used to elucidate the chemical structure of 1. The tubular structure formation in HUVECs was assessed by Mayer's hematoxylin staining. The migration of A2780 cells was evaluated using the scratch wound healing assay. Results: HUVECs treated with 1 had the statistically significant decrease in tubular structure formation compared to the HUVECs treated with compounds 2-8. This effect was enhanced by co-treatment with inhibitors for phosphatidylinositol 3-kinase (PI3K) (LY294002) and extracellular signal-regulated kinase (ERK) (U0126). Treatment with 1 decreased the expression of phosphorylation of ERK, PI3K, vascular endothelial growth factor receptor2 (VEGFR2), Akt, and mammalian target of rapamycin (mTOR). In addition, the ability of A2780 cells to cover the scratched area were also decreased. This effect was enhanced by co-treatment with U0126. Lastly, treatment with 1 decreased the phosphorylation of ERK, matrix metalloproteinase-9 (MMP-9), and MMP-2. Conclusion: These results suggest that ginsenglactone A is a potential inhibitor of HUVEC tubular structure formation and A2780 cellular migration, which may be helpful for understanding its anticancer mechanism.

Oddioside A, a New Phenolic Glycoside Isolated from the Fruits of Morus alba (Mulberry), Protects TNF-α-Induced Human Dermal Fibroblast Damage.

In our preliminary study, a hot water extract from the fruits of Morus alba (mulberry) inhibited the secretion of metalloproteinase-1 (MMP-1) against tumor necrosis factor-α (TNF-α)-stimulated human dermal fibroblasts (HDFs), and therefore we researched its active compounds. In the present study, a new phenolic glycoside (oddioside A, 1) and 21 known compounds (2-22) were isolated from the hot water extract from the fruits of M. alba by repeated chromatography. The chemical structure of the new compound 1 was elucidated by its spectroscopic data (1D- and 2D-NMR and HRMS) measurement and by acidic hydrolysis. The presence of sargentodoside E (2), eugenyl glucoside (6), 2-O-ß-d-glucopyranosyl-4,6-dihydroxybenzaldehyde (7), 7S,8R-erythro-7,9,9'-trihydroxy-3,3'-dimethoxy-8-O-4'-neolignan-4-O-ß-d-glucopyranoside (11), pinoresinol-4-O-ß-d-glucopyranoside (12), taxifolin-7-O-ß-d-glucopyranoside (20), and pinellic acid (21) were reported from M. alba for the first time in this study. The new compound oddioside A (1) suppressed the secretion of MMP-1 and increased collagen in TNF-α-stimulated HDFs. In addition, the phosphorylation of mitogen-activated protein kinases (MAPKs) was inhibited by oddioside A. In conclusion, the extract from fruits of M. alba and its constituent oddioside A may be a potential agent to prevent inflammation-related skin aging and other skin disorders.

Cytotoxic Properties of C17 Polyacetylenes from the Fresh Roots of Panax ginseng on Human Epithelial Ovarian Cancer Cells.

Although C17 polyacetylenes from Panax ginseng exhibit cytotoxic properties against various tumor cells, there have been few experiments on epithelial ovarian carcinoma cells. This study aimed to investigate the cytotoxic effects of C17 polyacetylenes from P. ginseng against ovarian cancer cell lines. Four unreported (1-4) and fifteen known (5-19) C17 polyacetylenes were obtained from the roots of P. ginseng using repeated chromatography (open column, MPLC, and preparative HPLC). The chemical structures of all the compounds were determined by analyzing their spectroscopic data (NMR, IR, and optical rotation) and HR-MS. The structures of new polyacetylenes were elucidated as (3S,8S,9R,10R)-(-)-heptadeca-9,10-epoxy-4,6-diyne-3,8-diyl diacetate (1), (3S,8S,9R,10R)-(-)-heptadeca-1-en-9,10-epoxy-4,6-diyne-3,8-diyl diacetate (2), (-)-haptadeca-9,10-epoxy-8-methoxy-4,6-diyne-3,11-diol (3), and (3R,9R,10R)-(+)-3-acetoxy-9,10-dihydroxyheptadeca-1-en-4,6-diyne (4), named ginsenoynes O, P, and Q, and 3-acetyl panaxytriol, respectively. Subsequently, in vitro experiments on A2780 and SKOV3 human epithelial ovarian carcinoma cells were performed to assess the cytotoxic properties of the isolates. Among the isolates, panaquinquecol 4 (15) exhibited the most remarkable cytotoxic effects on both human ovarian cancer cells A2780 (IC50 value of 7.60 µM) and SKOV3 (IC50 value of 27.53 µM). Therefore, C17 polyacetylenes derived from P. ginseng may warrant further investigation for their therapeutic potential in epithelial ovarian cancer.

The impact of sex steroids on osteonecrosis of the jaw.

Sex steroid hormones play a major role in bone homeostasis. Therefore, the use of sex hormones or drugs may increase the risk of osteonecrosis of the jaw (ONJ), a complication caused by damaged bone homeostasis. However, few are known the impact of medications changing sex hormone levels on ONJ. The pathophysiology of ONJ is not clearly understood and many hypotheses exist: cessation of bone remodeling caused by its anti-resorptive effect on osteoclasts; compromised microcirculation due to medication affecting angiogenesis, including bisphosphonate; and impairment of defense mechanism toward local infection. The use of high-dose intravenous bisphosphonate in cancer patients is associated with a high prevalence of ONJ. Exogenous estrogen or androgen replacement was reported to be associated with ONJ. Polycystic ovarian syndrome (PCOS) patients demonstrate an androgen excess status, and androgen overproduction serves as a protective factor in the bone mineral density of young women. To date, there are no reports of ONJ occurrence due to androgen overproduction. In contrast, few reports on the occurrence of ONJ due to estrogen deficiency induced by drugs, such as selective estrogen receptor modulator (SERM), aromatase inhibitors, and gonadotropin-releasing hormone (GnRH) agonists, are available. Thus, the role of sex steroids in the development of ONJ is not known. Further studies are required to demonstrate the exact role of sex steroids in bone homeostasis and ONJ progression. In this review, we will discuss the relationship between medication associated with sex steroids and ONJ.

Absolute Quantification of Isoflavones in the Flowers of Pueraria lobata by qHNMR.

Pueraria lobata (Willd.) Ohwi. is a widely used medicinal plant in Korea, China, and Japan. The flower of P. lobata (Puerariae Flos) contains various bioactive substances such as triterpenoidal saponins and isoflavonoids. In this study, we developed a quantitative analysis of the isoflavones of Puerariae Flos by quantitative proton nuclear magnetic resonance (qHNMR) spectroscopy using the internal calibrant (IC). From the qHNMR results, the isoflavone content was found to be 7.99% and 10.57% for the MeOH sonication extract (PLs) and the MeOH reflux extract (PLr) of Puerariae Flos, respectively. The quantified isoflavone content was validated using the conventional analytical method, high-performance liquid chromatography with ultraviolet detection (HPLC-UV). The present study shows that validated qHNMR spectroscopy is a reliable method for quantifying and standardizing the isoflavone content in Puerariae Flos.

Methyl Caffeate Isolated from the Flowers of Prunus persica (L.) Batsch Enhances Glucose-Stimulated Insulin Secretion.

Phenolic compounds from natural products are considered effective enhancers of insulin secretion to prevent and treat type 2 diabetes (T2DM). The flowers of Prunus persica (L.) Batsch also contain many phenolic compounds. In this study, the extract of flowers of P. persica (PRPE) exhibited an insulin secretion effect in a glucose-stimulated insulin secretion (GSIS) assay, which led us to isolate and identify the bioactive compound(s) responsible for these effects. Compounds isolated from PRPE were screened for their efficacy in INS-1 rat pancreatic ß-cells. Among them, caffeic acid (5), methyl caffeate (6), ferulic acid (7), chlorogenic acid (8), naringenin (11), nicotiflorin (12), and astragalin (13) isolated from PRPE increased GSIS without inducing cytotoxicity. Interestingly, the GSIS effect of methyl caffeate (6) as a phenolic compound was similar to gliclazide, an antidiabetic sulfonylurea drug. Western blot assay showed that methyl caffeate (6) enhanced the related signaling proteins of the activated pancreatic and duodenal homeobox-1 (PDX-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ), but also the phosphorylation of the total insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), and Akt, which influence ß-cell function and insulin secretion. This study provides evidence that methyl caffeate (6) isolated from PRPE may aid in the management of T2DM.

The Incidence and Risk Factors for Lumbar or Sciatic Scoliosis in Lumbar Disc Herniation and the Outcomes after Percutaneous Endoscopic Discectomy.

BACKGROUND: Some patients with lumbar herniated intervertebral disc disease (HIVD) suffer from both pain and lateral shift or trunk list. In addition to pain, patients have concerns regarding whether trunk list is reversible. Surgical treatment is performed when pain is intractable to conservative management, but a reversal of trunk list is an incidental outcome. Percutaneous lumbar endoscopic discectomy (PELD) is one of the surgical treatment options for lumbar HIVD, but no results concerning its effect on trunk list have been reported. OBJECTIVES: The objectives of the present study were to determine the incidence of, and risk factors for, trunk list scoliosis or lateral shift and to report the outcomes of trunk list after PELD. STUDY DESIGN: Retrospective case study. IRB No. H 1111-025-384 SETTING; University medical Center, Seoul, Korea. METHODS: We selected 164 patients who were less than 60 years old, complained of unilateral leg pain, and underwent PELD. We measured the maximum trunk shift from the central sacral vertical line (CSVL-max) on preoperative whole spine radiographs and classified trunk list as CSVL-max ≥ 10 mm. CSVL-max was measured on serial radiographs taken at one, 3, 6, and 12 months postoperatively in patients with trunk list. RESULTS: Twenty-nine patients (17.9%) had trunk list (M:F=10:19; mean age, 37.1 ± 11.24 years). Female gender (OR 4.28; 95% CI, 1.49-12.3) and HIVD at L4-5 (OR 5.6; 95% CI, 1.8-16.7) were risk factors for trunk list. Trunk list was normalized (CSVL-max < 10 mm) in 15 (52%) patients after PELD, and the median time for normalization was 3-6 months. Prognostic factors for the recovery of trunk list were not identified. LIMITATIONS: Selection bias should be considered in interpreting these results. CONCLUSION: Trunk list, scoliosis or lateral shift, was observed in 18% of the patients at the time of surgery. Female gender and L4-5 disc herniation were risk factors for trunk list. Trunk list was reversible in more than 50% of patients within 6 months of PELD.