Silkworm (Bombyx mori L.) Has Beneficial Effects on Menopausal Symptoms by Enhancing Estrogen Receptor Signaling in Ovariectomized Mice.

Existing hormone replacement therapy for menopause has drawbacks, necessitating new treatment agents. Silkworms have demonstrated estrogenic properties, offering promising alternatives. We assessed the therapeutic effects of freeze-dried silkworm powder (SWP) on menopausal symptoms using an ovariectomized (OVX) mouse model. The experimental design comprised a sham surgery group (Sham), an OVX control group, a low-dose SWP group post-OVX (80 mg/kg, OVX-SWP-L), a high-dose SWP group post-OVX (160 mg/kg, OVX-SWP-H), and an estradiol treatment group post-OVX (OVX-E2). Treatments were administered orally thrice weekly over eight weeks; body weight was monitored weekly. The SWP-treated groups (SWP-L and SWP-H) exhibited less weight gain and increased uterine thickness than the OVX control. Molecular analyses demonstrated that SWP significantly enhanced the phosphorylation of estrogen receptor alpha (ERα), ERK, and AKT. Furthermore, biochemical assays revealed reduced serum neutral lipids across all SWP treatment groups. Notably, HDL-cholesterol levels were significantly increased in the SWP-L group compared to the OVX group. Serum estradiol concentrations were elevated in all the SWP groups, with significant increases in the high-dose group. These findings indicate that SWP may promote the activation of estrogen receptor signaling and improve symptoms associated with estrogen deficiency during menopause.

Ameliorative Effects of Zingiber officinale Rosc on Antibiotic-Associated Diarrhea and Improvement in Intestinal Function.

The global increase in antibiotic consumption is related to increased adverse effects, such as antibiotic-associated diarrhea (AAD). This study investigated the chemical properties of Zingiber officinale Rosc (ZO) extract and its ameliorative effects using a lincomycin-induced AAD mouse model. Intestinal tissues were evaluated for the expression of lysozyme, claudin-1, and α-defensin-1, which are associated with intestinal homeostasis. The cecum was analyzed to assess the concentration of short-chain fatty acids (SCFAs). The chemical properties analysis of ZO extracts revealed the levels of total neutral sugars, acidic sugars, proteins, and polyphenols to be 86.4%, 8.8%, 4.0%, and 0.8%, respectively. Furthermore, the monosaccharide composition of ZO was determined to include glucose (97.3%) and galactose (2.7%). ZO extract administration ameliorated the impact of AAD and associated weight loss, and water intake also returned to normal. Moreover, treatment with ZO extract restored the expression levels of lysozyme, α-defensin-1, and claudin-1 to normal levels. The decreased SCFA levels due to induced AAD showed a return to normal levels. The results indicate that ZO extract improved AAD, strengthened the intestinal barrier, and normalized SCFA levels, showing that ZO extract possesses intestinal-function strengthening effects.

Gintonin Isolated from Ginseng Inhibits the Epithelial-Mesenchymal Transition Induced by TGF-ß in A549 Lung Cancer Cells.

Epithelial-to-mesenchymal transition (EM transition) is a process wherein epithelial cells lose their intrinsic characteristics and cell-cell junctions and differentiate into a mesenchymal phenotype. EM transition is an important feature of cancer invasion and metastasis. In this study, we aimed to investigate the inhibitory effect of gintonin (GT), an ingredient of ginseng, on EM transition using A549 cells. The proliferation of A549 cells was enhanced following treatment with 50, 75, and 100 µg/mL of GT. GT affected EM transition-induced gene and protein expression, specifically that of vimentin (Vim), N-cadherin (N-cad), zinc finger E-box-binding homeobox 1, and Twist in A549 cells. Furthermore, the transforming growth factor beta 1 (TGF-ß1)-induced phosphorylation of Smad2 and Smad3 was suppressed by GT treatment. Immunofluorescence staining also showed that GT treatment decreased the TGF-ß1-induced expression of Vim and N-cad in A549 cells. Therefore, GT may be used to suppress cancer cell metastasis via maintenance of the cell-cell junction's integrity. However, further studies are required to pave the way for its translation into clinical application in cancer therapeutics.

Synthesis and Biological Properties of Pyranocoumarin Derivatives as Potent Anti-Inflammatory Agents.

This study aimed to synthesize 23 coumarin derivatives and analyze their anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. A cytotoxicity test performed on LPS-induced RAW264.7 macrophages revealed that none of the 23 coumarin derivatives were cytotoxic. Among the 23 coumarin derivatives, coumarin derivative 2 showed the highest anti-inflammatory activity by significantly reducing nitric oxide production in a concentration-dependent manner. Coumarin derivative 2 inhibited the production of proinflammatory cytokines, including tumor necrosis factor alpha and interleukin-6, and decreased the expression level of each mRNA. In addition, it inhibited the phosphorylation of extracellular signal-regulated kinase, p38, c-Jun NH2-terminal kinase, nuclear factor kappa-B p65 (NF-κB p65), and inducible nitric oxide synthase. These results indicated that coumarin derivative 2 inhibited LPS-induced mitogen-activated protein kinase and NF-κB p65 signal transduction pathways in RAW264.7 cells, as well as proinflammatory cytokines and enzymes related to inflammatory responses, to exert anti-inflammatory effects. Coumarin derivative 2 showed potential for further development as an anti-inflammatory drug for the treatment of acute and chronic inflammatory diseases.

Characterization of macrophage activation after treatment with polysaccharides from ginseng according to heat processing.

The worldwide persistence of infectious diseases is a significant public health issue. Consequently, studying immunomodulatory ingredients present in natural products, such as ginseng, is important for developing new treatment options. Here, we extracted three different types of polysaccharides from white (P-WG), red (P-RG), and heat-processed (P-HPG) ginseng and analyzed their chemical properties and immunostimulatory activity against RAW 264.7 murine macrophages. Carbohydrates were the main components of all three polysaccharide types, while uronic acid and protein levels were relatively low. Chemical analysis indicated that the content of carbohydrates (total sugar) increased with processing temperature, while that of uronic acid decreased. Treatment with P-WG, P-RG or P-HPG stimulated nitric oxide (NO) production and increased tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 levels in RAW 264.7 macrophages, with P-WG showing the highest activity among the three polysaccharides. The expression of inducible NO synthase, which affects NO secretion, was highest in the macrophages treated with P-WG. Analysis of intracellular signaling pathways showed that mitogen-activated protein kinases (ERK, JNK, and p38) and NF-kB p65 were strongly phosphorylated by P-WG in macrophages but were only moderately phosphorylated by P-RG and P-HPG. Collectively, these results suggest that the polysaccharides isolated from ginseng undergo different changes in response to heat processing and display different chemical compositions and immune-enhancing activities.

Design, Synthesis, and Biological Evaluation of 3-Substituted-Indolin-2-One Derivatives as Potent Anti-Inflammatory Agents.

This study aimed to synthesize and evaluate the anti-inflammatory activity of 3-substituted-indolin-2-one derivatives. Cell viability of 3-substituted-indolin-2-one derivatives was measured with the EZ-Cytox reagent; interleukin (IL)-6, tumor necrosis factor (TNF)-α, and inducible NOS mRNA levels were measured using Taqman qRT-PCR; pro-inflammatory cytokine IL-6 and TNF-α levels were determined using ELISA kits; the phosphorylation of Akt, JNK, ERK, p38, p65, and IκB protein levels were measured by immunoblotting. Among the nineteen 3-substituted-indolin-2-one derivatives synthesized, 3-(3-hydroxyphenyl)-indolin-2-one showed the highest anti-inflammatory activity, inhibiting the nitric oxide production related to inflammation, suppressing the production of TNF-α and IL-6 in a concentration-dependent manner and mRNA expression. Moreover, 3-(3-hydroxyphenyl)-indolin-2-one significantly inhibited lipopolysaccharide (LPS)-induced signal pathways such as the Akt, MAPK, and NF-κB signaling pathways. Our findings revealed that a 3-substituted-indolin-2-one derivative, 3-(3-hydroxyphenyl)-indolin-2-one, possesses excellent anti-inflammatory activity and can be considered for future research.

Preparation of inhalable N-acetylcysteine-loaded magnetite chitosan microparticles for nitrate adsorption in particulate matter.

Airborne particulate matter has been designated as a class 1 carcinogen by the World Health Organization. Nitrate is a toxic substance that accounts for a large proportion of particulate matter, and nitrate toxicity has long been reported. In this study, we aimed to optimize the adsorption and removal of particulate matter containing nitrate for effective elimination by the lungs. To this end, particles were designed to optimize the inhalation and removal efficiencies. These particles were prepared as chitosan-based particles containing N-acetylcysteine by using emulsion diffusion methods. Chitosan adsorbs nitrate, while N-acetylcysteine dissolves mucus. This removal mechanism has been found to occur in various in vitro models that mimic respiratory environments and in vivo models. In particular, the removal of exogenous substances, such as particulate matter, by the motility of respiratory cilia through mucolytic effect was investigated. This new approach for the adsorption and elimination of toxic substances entering the lungs represents an alternative defense mechanism against exposure to nitrates from air pollution.

Mitigation of Gastric Damage Using Cinnamomum cassia Extract: Network Pharmacological Analysis of Active Compounds and Protection Effects in Rats.

Gastritis is a common disease worldwide that is caused by various causes such as eating habits, smoking, severe stress, and heavy drinking, as well as Helicobacter pylori infections and non-steroidal anti-inflammatory drugs. Cinnamomum cassia is a tropical aromatic evergreen tree commonly used as a natural medicine in Asia and as a functional food ingredient. Studies have reported this species' anti-obesity, anti-diabetic, and cardiovascular disease suppression effects. We evaluated the potential effects of C. cassia using non-steroidal anti-inflammatory drugs (NSAIDs), ethanol (EtOH), and ethanol/hydrochloric acid (HCl)-induced gastric mucosal injury models. C. cassia extracts reduced the area of gastric mucosa injury caused by indomethacin, NSAID, EtOH, and EtOH/HCl. We also applied a network pharmacology-based approach to identify the active compounds, potential targets, and pharmacological mechanisms of C. cassia against gastritis. Through a network pharmacology analysis, 10 key components were predicted as anti-gastritis effect-related compounds of C. cassia among 51 expected active compounds. The NF-κB signaling pathway, a widely known inflammatory response mechanism, comprised a major signaling pathway within the network pharmacology analysis. These results suggest that the anti-gastritis activities of C. cassia may be induced via the anti-inflammatory effects of key components, which suppress the inflammation-related genes and signaling pathways identified in this study.

Composition analysis and oral administered effects on dextran sulfate sodium-induced colitis of galactooligosaccharides bioconverted by Bacillus circulans.

Galactooligosaccharides have been known to have many health benefits as prebiotic ingredients. In this study, we examined the anti-inflammatory activity of the galactooligosaccharide, NeoGOS-P70 (Korean commercial product), in a dextran sodium sulfate-induced colitis model. Next, we performed compositional characterization of NeoGOS-P70, which confirmed that it was a 77.4% high-purity GOS products, including a large amount of 4'-galactosyllactose. Further experiments in DSS-induced colitis model showed that oral administration of NeoGOS-P70 could significantly improve DSS-induced colitis symptoms, such as weight loss, reduction in colon shortening, and suppression of inflammatory mediators, including interleukin-6, tumor necrosis factor-α, and myeloperoxidase secretion from colon of ulcerative colitis mice. Histological analysis of mucin expression in colon tissue revealed the protective effects of NeoGOS-P70. These results suggest the potential of the novel GOS, NeoGOS-P70, as an anti-ulcerative colitis agent that could regulate inflammatory responses.

Inhibition of A549 Lung Cancer Cell Migration and Invasion by Ent-Caprolactin C via the Suppression of Transforming Growth Factor-ß-Induced Epithelial-Mesenchymal Transition.

The epithelial-mesenchymal transition (EMT) of cancer cells is a crucial process in cancer cell metastasis. An Aquimarina sp. MC085 extract was found to inhibit A549 human lung cancer cell invasion, and caprolactin C (1), a new natural product, α-amino-ε-caprolactam linked to 3-methyl butanoic acid, was purified through bioactivity-guided isolation of the extract. Furthermore, its enantiomeric compound, ent-caprolactin C (2), was synthesized. Both 1 and 2 inhibited the invasion and γ-irradiation-induced migration of A549 cells. In transforming growth factor-ß (TGF-ß)-treated A549 cells, 2 inhibited the phosphorylation of Smad2/3 and suppressed the EMT cell marker proteins (N-cadherin, ß-catenin, and vimentin), as well as the related messenger ribonucleic acid expression (N-cadherin, matrix metalloproteinase-9, Snail, and vimentin), while compound 1 did not suppress Smad2/3 phosphorylation and the expression of EMT cell markers. Therefore, compound 2 could be a potential candidate for antimetastatic agent development, because it suppresses TGF-ß-induced EMT.

Identification of the Active Ingredient and Beneficial Effects of Vitex rotundifolia Fruits on Menopausal Symptoms in Ovariectomized Rats.

Estrogen replacement therapy is a treatment to relieve the symptoms of menopause. Many studies suggest that natural bioactive ingredients from plants resemble estrogen in structure and biological functions and can relieve symptoms of menopause. The fruit of V. rotundifolia, called "Man HyungJa" in Korean, is a traditional medicine used to treat headache, migraine, eye pain, neuralgia, and premenstrual syndrome in Korea and China. The aim of the present study was to confirm that V. rotundifolia fruit extract (VFE) exerts biological functions similar to those of estrogen in menopausal syndrome. We investigated its in vitro effects on MCF-7 cells and in vivo estrogen-like effects on weight gain and uterine contraction in ovariectomized rats. Using the polar extract, the active constituents of VFE (artemetin, vitexicarpin, hesperidin, luteolin, vitexin, and vanillic acid) with estrogen-like activity were identified in MCF-7 cells. In animal experiments, the efficacy of VFE in ameliorating body weight gain was similar to that of estrogen, as evidenced from improvements in uterine atrophy. Vitexin and vitexicarpin are suggested as the active constituents of V. rotundifolia fruits.

Inhibitory Effects of Pectic Polysaccharide Isolated from Diospyros kaki Leaves on Tumor Cell Angiogenesis via VEGF and MMP-9 Regulation.

Persimmon leaves are an attractive source of phytochemicals with potential health benefits. However, there are only a few reports on the chemical properties and biological activity of the polysaccharide fractions (PLE-I-III) of persimmon leaves. We evaluated the angiogenesis-inhibiting ability of pectic-polysaccharides. The molecular weight of PLEs was determined using a high-performance size-exclusion chromatography system. Tube formation assay of human umbilical vein endothelial cells (HUVECs) was performed using Matrigel-coated 96-well plates. Matrix metalloproteinase (MMP-9), vascular endothelial growth factor (VEGF), PI3K, Akt, and p38 phosphorylation levels were determined using Western blotting; VEGF and MMP-9 transcript levels were measured using SYBR Green qRT-PCR. PLE-I-III significantly inhibited HUVEC tube formation at 12.5 and 25 µg/mL. Among them, PLE-II showed the strongest anti-tube formation activity, and the mRNA/protein expression of angiogenesis-related factors (VEGF/MMP-9) was significantly reduced by PLE-II. PLE-II also suppressed the phosphorylation of PI3K/AKT and p38, JNK, and NF-κB p65 in HUVECs. These results suggest that the polysaccharide PLE-II isolated from persimmon leaves inhibited VEGF and MMP-9 expression in HUVECs via regulation of PI3K/AKT, p38, JNK, and NF-κB p65 signaling pathways.

Signaling pathway and structural features of macrophage-activating pectic polysaccharide from Korean citrus, Cheongkyool peels.

To characterize the immuno-stimulating ingredient from the Korean citrus, Cheongkyool, a crude polysaccharide (CCE-0) was isolated from the pectinase digests of Cheongkyool peels, from which the complex polysaccharide CCE-I was purified to homogeneity by gel filtration. CCE-I highly enhanced the production of IL-6, TNF-α, and NO in RAW 264.7 cell lines. It augmented the mRNA expression of IL-6, TNF-α, and iNOS in a dose-dependent manner. Moreover, CCE-I dose-dependently induced phosphorylation of MAPKs and NF-κB related proteins and led to the nuclear translocation of p65. The effect of CCE-I on NO and IL-6 production was suppressed by treatment with specific antibodies for TLR2, TLR4, and scavenger receptors. Conversely, the primary structure of CCE-I that exhibited potent immunostimulatory activity was characterized by sugar composition, linkage analysis, and oligosaccharide analysis after ß-elimination. The results suggested that CCE-I may be a rhamnogalacturonan-I type, highly branched polysaccharide with short arabinan and galactan side chains.

A Hydroxypropyl Methylcellulose-Based Solid Dispersion of Curcumin with Enhanced Bioavailability and its Hepatoprotective Activity.

Curcumin is a polyphenol compound derived from the rhizomes of Curcuma longa that exhibits antioxidant, anti-inflammatory, anticancer, and antimicrobial properties. However, its low solubility in aqueous solutions, low absorption following oral administration, and rapid degradation limit its use as a functional food material. In this study, a hydroxypropyl methylcellulose-based solid dispersion of curcumin (DW-CUR 20) was prepared and its bioavailability was evaluated. In addition, its therapeutic efficacy as a hepatoprotective agent was investigated using the model of tert-butyl hydroperoxide (t-BHP)-induced hepatocyte damage. The rat plasma pharmacokinetic study showed that the oral curcumin bioavailability of DW-CUR 20 significantly increased compared to that of non-formulated curcumin. DW-CUR 20 showed a concentration-dependent hepatocyte protective effect on t-BHP-induced HepG2 cells. DW-CUR 20 inhibited the release of lactate dehydrogenase and decreased apoptosis-related proteins such as Poly (ADP-ribose) polymerase, cleaved caspase-7 and cleaved caspase-8 on t-BHP-treated HepG2 cells. These findings suggest that DW-CUR 20 could be a promising formulation for enhancing the therapeutic efficiency of curcumin and for improving the safety.

Analysis and Identification of Active Compounds from Gami-Soyosan Toxic to MCF-7 Human Breast Adenocarcinoma Cells.

Gami-soyosan is a medicinal herbal formulation prescribed for the treatment of menopausal symptoms, including hot flashes and osteoporosis. Gami-soyosan is also used to treat similar symptoms experienced by patients with breast cancer. The incidence of breast cancer in women receiving hormone replacement therapy is a big burden. However, little is known about the components and their mechanism of action that exhibit these beneficial effects of Gami-soyosan. The aim of this study was to simultaneously analyze compounds of Gami-soyosan, and determine their cytotoxic effects on estrogen receptor (ER)-positive MCF-7 human breast adenocarcinoma cells. We established a simultaneous analysis method of 18 compounds contained in Gami-soyosan and found that, among the various compounds in Gami-soyosan, gallic acid (1), decursin (17), and decursinol angelate (18) suppressed the viability of MCF-7 cells. Gallic acid (1), decursin (17), and decursinol angelate (18) induced apoptotic cell death and significantly increased poly (ADP-ribose) polymerase (PARP) cleavage and the Bcl-2-associated X protein/ B-cell lymphoma 2 (Bax/Bcl-2) ratio. Decursin (17) increased the expression of cleaved caspases-8, -9, -7, and -3. Decursinol angelate (18) increased the expression of cleaved caspase-8 and -7. These three components altered the different apoptosis signal pathways. Collectively, gallic acid (1), decursin (17), and decursinol angelate (18) may be used to inhibit cell proliferation synergistically in patients with ER-positive breast cancer.

Signaling pathways associated with macrophage-activating polysaccharides purified from fermented barley.

Barley is commonly used in many food and health products. We have previously demonstrated the macrophage-stimulating properties of polysaccharides derived from fermented barley. In this study, three polysaccharide fractions (BF-I-III) were purified from fermented barley and their monosaccharide composition was analyzed. Their immune-stimulatory activities and intracellular signaling pathways were also studied in RAW264.7 cells. Among the three fractions, BF-I exhibited enhanced macrophage activation properties, such as inducing the production of IL-6, IL-12, and TNF-α. However, BF-II and BF-III showed moderate effects on RAW 264.7 cells. BF-I treatment led to the phosphorylation of MAPKs, NF-κB, and c-Jun (major component of AP-1 transcription factor) and induced the nuclear translocation of p65 in RAW264.7 cells. In addition, experiments with neutralizing antibodies showed that Dectin-1, toll-like receptor (TLR) 4, scavenge receptor (SR), and CD14 were mainly involved in the stimulation of nitric oxide (NO) production by BF-I which was suppressed by the inhibition of JNK phosphorylation. These findings suggest that BF-I, isolated from fermented barley, has an immune potentiation activity on macrophages, where it activates the JNK signaling pathway via several macrophage receptors including dectin-1, TLR4, SR, and CD14.

Preparation of Herbal Formulation for Inflammatory Bowel Disease Based on In Vitro Screening and In Vivo Evaluation in a Mouse Model of Experimental Colitis.

Many medicinal plants have been used traditionally in East Asia for the treatment of gastrointestinal disease and inflammation. The aim of this study was to evaluate the anti-inflammatory activity of 350 extracts (175 water extracts and 175 ethanol extracts) from 71 single plants, 97 mixtures of two plants, and seven formulations based on traditional medicine, to find herbal formulations to treat inflammatory bowel disease (IBD). In the in vitro screening, nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels were determined in LPS-treated RAW264.7 cells and the TNF-α induced monocyte-epithelial cell adhesion assay was used for the evaluation of the anti-inflammatory activity of the compounds. Dextran sulfate sodium (DSS)-induced colitis model and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model were used to evaluate the therapeutic effect against IBD of the samples selected from the in vitro screening. KM1608, composed of Zingiber officinale, Terminalia chebula and Aucklandia lappa, was prepared based on the screening experiments. The oral administration of KM1608 significantly attenuated the severity of colitis symptoms, such as weight loss, diarrhea, and rectal bleeding, in TNBS-induced colitis. In addition, inflammatory mediators, such as myeloperoxidase, TNF-α, and IL-6 levels decreased in the lysate of colon tissues treated with KM1608. Collectively, KM1608 ameliorated colitis through the regulation of inflammatory responses within the colon, which indicated that KM1608 had potential for the treatment of IBD.

Anti-Atopic Effect of Acorn Shell Extract on Atopic Dermatitis-Like Lesions in Mice and Its Active Phytochemicals.

To investigate the potential effects of acorn shells on atopic dermatitis (AD), we utilized oxazolone (OX)- or 2,4-dinitrochlorobenzene (DNCB)-induced AD-like lesion mouse models. Our research demonstrates that Acorn shell extract (ASE) improved the progression of AD-like lesions, including swelling, which were induced by oxazolone on Balb/c mouse ears. Additionally, ASE significantly decreased the ear thickness (OX: 0.42 ± 0.01 mm, OX-ASE: 0.32 ± 0.02 mm) and epidermal thickness (OX: 75.3 ± 32.6 µm, OX-ASE: 46.1 ± 13.4 µm). The continuous DNCB-induced AD mouse model in SKH-1 hairless mice demonstrated that ASE improved AD-like symptoms, including the recovery of skin barrier dysfunction, Immunoglobulin E hyperproduction (DNCB: 340.1 ± 66.8 ng/mL, DNCB-ASE: 234.8 ± 32.9 ng/mL) and an increase in epidermal thickness (DNCB: 96.4 ± 21.9 µm, DNCB-ASE: 52.4 ± 16.3 µm). In addition, we found that ASE suppressed the levels of AD-involved cytokines, such as Tumor Necrosis Factor α, IL-1ß, IL-25 and IL-33 in both animal models. Furthermore, gallic acid and ellagic acid isolated from ASE suppressed ß-hexosaminidase release and IL-4 expression in RBL-2H3 cells. The acorn shell and its active phytochemicals have potential as a new remedy for the improvement of atopic dermatitis and other inflammatory diseases.

Application of microwave-irradiation technique in deglycosylation of ginsenosides for improving apoptosis induction in human melanoma SK-MEL-2 cells.

To increase the contents of medicinally effective ginsenosides, we used high-temperature and high-pressure thermal processing of ginseng by exposing it to microwave irradiation. To determine the anti-melanoma effect, the malignant melanoma SK-MEL-2 cell line was treated with an extract of microwave-irradiated ginseng. Microwave irradiation caused changes in the ginsenoside contents: the amounts of ginsenosides Rg1, Re, Rb1, Rb2, Rc, and Rd were disappeared, while those of less polar ginsenosides, such as Rg3, Rg5, and Rk1, were increased. In particular, the contents of Rk1 and Rg5 markedly increased. Melanoma cells treated with the microwave-irradiated ginseng extract showed markedly increased cell death. The results indicate that the microwave-irradiated ginseng extract induced melanoma cell death via the apoptotic pathway and that the cytotoxic effect of the microwave-irradiated ginseng extract is attributable to the increased contents of specific ginsenosides.