Kiwon Jung

Potentially hepatoprotective glycolipid constituents of Lycium chinense fruits.

Further investigation ofLycium chinense fruits gave a mixture of -O-palmitoyl)- and (6’-O-stearoyl)-β-sitosterol-S-O-β-D-glucopyranoside (1) and two glycolipids, 1-O-(9Z,12Z, I5Z-octa-decatrienoyl)-2-O-(9Z,12Z,15Z-octadecatrienoyl)-3-O-β-D-galactopyranosyl glycerol (2) and 1 -O-(9Z, 12Z-octadecadienoyl)-2-O-(9Z, 12Z, 15Z-octadecatrienoy-3-S-O-β-D-galactopyranosyl glycerol (3). These compounds were newly isolated as constituents ofL. chinense.

Anti-inflammatory properties of a triterpenoidal glycoside from Momordica cochinchinensis in LPS-stimulated macrophages.

Two triterpenoidal saponins were isolated from the seeds of Momordica cochinchinensis Sprenger (Cucurbitaceae). Identification of chemical structures has been performed by 1H- and 13C-NMR spectroscopy and gas chromatography (GC). One of the saponins is a new gypsogenin glycoside, named as gypsogenin 3-O-β-D-galactopyranosyl(1→2)-[α-L-rhamnopyranosyl(1→3)]-β-D-glucuronopyranoside (compound 1), which is reported for the first time from natural resources. The other saponin is a quillaic acid glycoside (compound 2), which showed anti-inflammatory activities in RAW 264.7 cells. The mechanistic understanding of anti-inflammatory activities demonstrates that compound 2 inhibits lipopolysaccharide-induced expression of nitric oxide and IL-6 via NF-κB pathway.

Anti-gastritis and wound healing effects of Momordicae Semen extract and its active component

Momordicae Semen, Momordica cochinchinensis Springer (Cucurbitaceae), has long been known to effectively relieve boils, rheumatic pain, and hemorrhoids. In this study, we investigated whether Momordicae Semen extract (MSE) has anti-gastritis effects in various rodent models and also explored possible mechanisms for the gastroprotective effects of MSE. MSE provided remarkable protective effects, comparable to those of rebamipide, in ethanol- and diclofenac-induced acute gastritis. In addition, it has demonstrated protective effect in a Helicobacter pylori-insulted chronic gastritis model. MSE also showed wound healing effect on cutaneous injury of mice and stimulated calcitonin gene-related peptide and somatostatin receptors, which may be related to its anti-gastritis effects. In a single oral dose toxicity study, the approximate lethal dose of MSE was determined at >2000 mg/kg/day. The NOAEL was set to be 2000 mg/kg/day from the repeated oral dose toxicity study. Moreover, momordica saponin I, a major ingredient of MSE, treatment decreased gastric mucosa damage indices in the ethanol- and diclofenac-induced acute gastritis models. The results suggest that MSE could be a promising gastroprotective herbal medicine and momordica saponin I might be used as an active marker compound for MSE.

Src/Syk-Targeted Anti-Inflammatory Actions of Triterpenoidal Saponins from Gac (Momordica cochinchinensis) Seeds

Momordica cochinchinensis Spreng (family Cucurbitaceae), also known as gac, or red melon, is an edible Southeast Asian fruit valued for its nutritional and medicinal properties. Specifically, Momordicae Semen, the seeds of the gac fruit, is used in traditional Chinese medicine to treat boils, rheumatic pain, muscle spasm, hemorrhoids, and hemangiomas. In this study, a chemical investigation into a gac seed ethanol (EtOH) extract resulted in the identification of three triterpenoidal saponins (1-3), which were investigated for their anti-inflammatory effects. Among the saponins, momordica saponin I (compound 3) reduced the production of nitric oxide (NO) in LPS-activated RAW264.7 cells without inducing cytotoxicity. The mRNA levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were decreased by momordica saponin I. Additionally, the translocation of p65 and p50 (subunits of the transcription factor NF-[Formula: see text]B) into the nucleus was remarkably inhibited. Furthermore, the phosphorylation levels of inflammatory signaling proteins (I[Formula: see text]B[Formula: see text], Src, and Syk) known to be upstream regulatory molecules of p65 were decreased under momordica saponin I-treated conditions. The molecular targets of momordica saponin I were confirmed in overexpression experiments and through immunoblot analyses with Src and Syk. This study provides evidence that momordica saponin I could be beneficial in treating inflammatory diseases, and should be considered a bioactive immunomodulatory agent with anti-inflammatory properties.

Anti-inflammatory effects and corresponding mechanisms of cirsimaritin extracted from Cirsium japonicum var. maackii Maxim

In this study, we investigated the anti-inflammatory effects and mechanisms of cirsimaritin isolated from an ethanol extract of the aerial parts of Cirsium japonicum var. maackii Maxim. using RAW264.7 cells. The extract and its flavonoid cirsimaritin inhibited nitric oxide (NO) production and inducible nitric oxide synthase expression in RAW264.7 cells. Cirsimaritin inhibited interleukin-6, tumor necrosis factor-α, and NO production in a concentration-dependent manner in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. From a western blot study, pretreatment with cirsimaritin inhibited phosphorylation/degradation of IκBα and phosphorylation of Akt in LPS-stimulated RAW264.7 cells. Moreover, cirsimaritin suppressed activation of LPS-induced transcription factors, such as c-fos and signal transducer and activator of transcription 3 (STAT3), in RAW264.7 cells. Collectively, these results show that cirsimaritin possesses anti-inflammatory activity, which is regulated by inhibition of c-fos and STAT3 phosphorylation in RAW264.7 cells.

Renoprotective chemical constituents from an edible mushroom, Pleurotus cornucopiae in cisplatin-induced nephrotoxicity

Pleurotus cornucopiae (Pleurotaceae) is an edible and medicinal mushroom widely distributed in Korea, China, and Japan. The MeOH extract of the fruiting bodies of P. cornucopiae showed renoprotective effects against cisplatin-induced kidney cell damage. Chemical investigation of the MeOH extract led to the isolation and identification of 12 compounds including noransine (1), uridine (2), uracil (3), (3β, 5α, 6β, 22E, 24S) -ergosta-7, 22-diene-3, 5, 6, 9-tetrol (4), (22E,24S)-ergosta-7,22-diene-3β,5α,6β-triol (5), (22E,24R)-ergosta-8(14),22-diene-3β,5α,6β,7α-tetrol (6), cerebroside B (7), (2R) -N- [(1S, 2R, 3E, 7E) -1- [(β-d-glucopyranosyloxy) methyl] -2-hydroxy-8-methyl-3, 7-heptadecadien-1-yl] -2-hydroxy-heptadecanamide (8), cerebroside D (9), nicotinamide (10), 1,2-bis(hydroxymethyl)-4,5-dimethoxybenzene (11), and benzoic acid (12). Among them, compounds 1 and 11 were isolated as naturally occurring products for the first time, though they were reported as synthetic products in previous papers. All of the compounds (except 8 and 11) abrogated cisplatin-induced LLC-PK1 cell damage in a dose-dependent manner. Of special note, compounds 2, 5, 6, and 12 ameliorated cisplatin-induced nephrotoxicity to 80% of the control value at 10μM. The protective effects of compounds 2, 5, 6, and 12 were mediated via the deactivation of JNK-caspase 3 apoptotic cascade. This study is the first to demonstrate that the chemical constituents of P. cornucopiae display renoprotective effects against anticancer drug-induced damage in kidney cells.

Protective effect of α-mangostin against iodixanol-induced apoptotic damage in LLC-PK1 cells.

Radiographic contrast media facilitate the visibility of internal body structures, but its use to patients with lowered renal function needs to be careful because of severe side effect in kidney. The present study aims to evaluate potential protective effect and mechanism of Alpha mangostin (α-mangostin) against contrast-induced apoptotic damage in LLC-PK1 cells. As a result, α-mangostin in non-toxic concentrations improved the viability of the iodixanol-treated cells up to 90.42% against contrast-induced damage in LLC-PK1 cells. Iodixanol treatment increased the phosphorylation of p38, ERK and cleavage of caspase-3 in LLC-PK1 cells, which were significantly decreased by co-treatment with α-mangostin (2.5 and 5μM). The protective effect of α-mangostin on contrast-induced apoptotic damage was mediated by the inhibition of MAPKs and caspase activation.

Protective effect and mechanism of action of saponins isolated from the seeds of gac (Momordica cochinchinensis Spreng.) against cisplatin-induced damage in LLC-PK1 kidney cells

This study was performed to investigate the renoprotective effect and mechanism of Momordicae Semen, gac seeds, against the cisplatin-induced damage in LLC-PK1 kidney cells. In order to identify the active components, three major saponins were isolated from extract of the gac seed, gypsogenin 3-O-β-d-galactopyranosyl(1→2)-[α-L-rhamnopyranosyl(1→3)]-β-d-glucuronopyranoside (1), quillaic acid 3-O-β-D-galactopyranosyl(1→2)-[α-L-rhamnopyranosyl(1→3)]-β-D-glucuronopyranoside (2), and momordica saponin I (3). Compounds 1 and 2 ameliorated cisplatin-induced nephrotoxicity up to 80% of the control value at both 5 and 25μM. Phosphorylation of MAPKs was decreased along cisplatin treatment after treatment with compounds 1 and 2. These results show that blocking the MAPKs signaling cascade plays a critical role in mediating the renoprotective effect of Momordicae Semen extract and compounds 1 and 2.

Poloxamer-Based Thermoreversible Gel for Topical Delivery of Emodin: Influence of P407 and P188 on Solubility of Emodin and Its Application in Cellular Activity Screening

Emodin is a component in a Chinese herb, Rheum officinale Baill, traditionally used for diabetes and anticancer. Its poor solubility is one of the major challenges to pharmaceutical scientists. We previously reported on thermoreversible gel formulations based on poloxamer for the topical delivery of emodin. The present study was to understand the effect of poloxamer type on emodin solubility and its application in cellular activity screening. Various gel formulations composed of poloxamer 407 (P407), poloxamer 188 (P188) and PEG400 were prepared and evaluated. Major evaluation parameters were the gelation temperature (Tgel) and solubility of emodin. The emodin solubility increased with increasing poloxamer concentration and the Tgel was modulated by the proper combination of P407. In particular, this study showed that the amount of P407 in thermoreversible poloxamer gel (PG) was the dominant factor in enhancing solubility and P188 was effective at fixing gelation temperature in the desired range. A thermoreversible emodin PG was selected as the proper composition with the liquid state at room temperature and gel state at body temperature. The gel showed the solubility enhancement of emodin at least 100-fold compared to 10% ethanol or water. The thermoreversible formulation was applied for in vitro cellular activity screening in the human dermal fibroblast cell line and DLD-1 colon cancer cell line after dilution with cell culture media. The thermoreversible gel formulation remained as a clear solution in the microplate, which allowed reliable cellular activity screening. In contrast, emodin solution in ethanol or DMSO showed precipitation at the corresponding emodin concentration, complicating data interpretation. In conclusion, the gel formulation is proposed as a useful prototype topical formulation for testing emodin in vivo as well as in vitro.

Beneficial effects of Panax ginseng for the treatment and prevention of neurodegenerative diseases: past findings and future directions

In recent years, several therapeutic drugs have been rationally designed and synthesized based on the novel knowledge gained from investigating the actions of biologically active chemicals derived from foods, plants, and medicinal herbs. One of the major advantages of these naturalistic chemicals is their ability to interact with multiple targets in the body resulting in a combined beneficial effect. Ginseng is a perennial herb (Araliaceae family), a species within the genus Panax, and a highly valued and popular medicinal plant. Evidence for the medicinal and health benefits of Panax ginseng and its components in preventing neurodegeneration has increased significantly in the past decade. The beneficial effects of P. ginseng on neurodegenerative diseases have been attributed primarily to the antioxidative and immunomodulatory activities of its ginsenoside components. Mechanistic studies on the neuroprotective effects of ginsenosides revealed that they act not only as antioxidants but also as modulators of intracellular neuronal signaling and metabolism, cell survival/death genes, and mitochondrial function. The goal of the present paper is to provide a brief review of recent knowledge and developments concerning the beneficial effects as well as the mechanism of action of P. ginseng and its components in the treatment and prevention of neurodegenerative diseases.