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Free fatty acid-induced lipotoxicity is considered to play an important role in pancreatic β-cell dysfunction. The effect of ginsenosides on palmitic acid-induced pancreatic beta-cells cell death and failure of glucose-stimulated secretion of insulin (GSIS) was evaluated in this study.

Here, we aimed to assess the inhibitory effect of a new compound from Panax ginsengon the migration of human ovarian cancer cells and tube formation of human umbilical vein endothelial cells (HUVECs).

Aloe-emodin, an anthraquinone compound naturally derived from Rheum undulatumL., has gained extensive research attention owing to its various pharmacological effects, including its potential as an anticancer, antivirus, anti-inflammatory, antibacterial, and anti-parasitic agent. It has demonstrated notable inhibitory effects against various types of cancer and cancer cells. Prostate cancer is among the most commonly identified cancers globally and remains a leading cause of cancer-associated deaths in men, often presenting challenges in early detection due to its asymptomatic nature during initial stages. The aim of present study was to determine the biological activity of aloe-emodin obtained from Rheum undulatumL. involving activation of the p53-dependent pathway in certain human prostate cancer cell lines. We explored the mechanisms underlying the anticancer effects of aloe-emodin using LNCaP cells, which include p53-wild type and phosphatase and tensin homolog-deficient mutated genes, a widely studied model in genomic research. Aloe-emodin induced apoptosis in LNCaP cells through several mechanisms, including upregulation of the cleavage of caspase-8 (a cross-linked promoter of cell death signals), phosphorylation of p53 at serine 15, DNA fragmentation, cleavage of poly [ADP-ribose] polymerase, and promotion of cell death. These findings strongly indicated that aloe-emodin's anticancer properties in human prostate cancer involve the activation of p53-induced cellular senescence. Conclusively, the findings of this study imply that aloe-emodin extracted from Rheum undulatumL.is a potential therapeutic compound for adjuvant chemotherapy that induces apoptosis and pyroptosis, an innate immune response, in preventing the progression of precancerous lesions in patients with prostate cancer.

Fourteen azaphilone-type polyketides (1–14), including nine new ones (1–6and 8–10), were isolated from cultures of Vitex rotundifolia-associated Penicilliumsp. JVF17, and their structures were determined by spectroscopic analysis together with computational methods and chemical reactions. Neuroprotective effects of the isolated compounds were evaluated against glutamate-induced neurotoxicity. Treatment with compounds 3, 6, 7, and 11–14increased cell viabilities of hippocampal neuronal cells damaged by glutamate, with compound 12being the most potent. Compound 12markedly decreased intracellular Ca2+and nuclear condensation levels. Mechanistically, molecular markers of apoptosis induced by treatment with glutamate, i.e., phosphorylation of MAPKs and elevated Bax/Bcl-2 expression ratio, were significantly lowered by compound 12. The azaphilones with an isoquinoline core structure were more active than those with pyranoquinones, but N-substitution decreased the activity. This study, including the structure–activity relationship, indicates that the azaphilone scaffold is a promising lead toward the development of novel neuroprotective agents.

A new phenolic glucoside, (7E,9E)-3-hydroxyavenalumic acid-3-O-[6′-O-(E)-caffeoyl]-β-d-glucopyranoside (1), and three new acetylated flavone glycosides, acacetin-7-O-[β-d-glucopyranosyl(1″″→2″)-4‴-O-acetyl-α-l-rhamnopyranosyl(1‴→6″)]-β-d-glucopyranoside (3), acacetin-7-O-[6″″-O-acetyl-β-d-glucopyranosyl(1″″→2″)-3‴-O-acetyl-α-l-rhamnopyranosyl(1‴→6″)]-β-d-glucopyranoside (5), and acacetin-7-O-[3″″,6″″-di-O-acetyl-β-d-glucopyranosyl(1″″→2″)-4‴-O-acetyl-α-l-rhamnopyranosyl(1‴→6″)]-β-d-glucopyranoside (7), as well as 34 known compounds (2, 4, 6, and 8–38) were isolated from the aerial parts of Elsholtzia ciliata. The chemical structures of the new compounds were determined by spectroscopic/spectrometric data interpretation using NMR and HRESIMS. The neuroprotective effect of the isolated compounds was evaluated by a cell viability assay on HT22 murine hippocampal neuronal cells. Among them, 23 compounds, including new substances 1and 3, exhibited neuroprotective effects against glutamate-induced HT22 cell death. In particular, compounds 2, 16, 17, 20, 22, 28, 29, and 31presented potent neuroprotective effects with EC50values of 1.5–8.3 μM.

Calvatia nipponicais an extremely rare mushroom with a limited number of studies on its chemical components and biological activities published. Here we report the isolation of a novel sterol, calvatianone (1), possessing a 6/5/6/5-fused ring system with a contracted tetrahydrofuran B-ring, and four known steroids (2–5) from the fruiting bodies of C. nipponica. The structure of calvatianone including its absolute configuration was determined by NMR spectroscopic analyses, HR-ESIMS, gauge-including atomic orbital NMR chemical shift calculations, and ECD calculations. Ergosterol peroxide (3) and cyathisterol (4) suppressed the cell viability increase induced by 17β-estradiol in MCF-7 breast cancer cell lines, suggesting a possible approach for these compounds to serve as ERα antagonists.

The absolute configuration and corrected NMR assignment of 17-hydroxycyclooctatin isolated from Streptomycessp. M56 recovered from a nest of South African Macrotermes natalensistermites are reported. 17-Hydroxycyclooctatin is a unique tricyclic diterpene (C20) consisting of a fused 5–8–5 ring system, and in this study, its structure was unambiguously determined by a combination of HR-ESIMS and 1D and 2D NMR spectroscopic experiments to produce corrected NMR assignments. The absolute configuration of 17-hydroxycyclooctatin is reported for the first time in the current study using chemical reactions and quantum chemical ECD calculations. The corrected NMR assignments were verified using a gauge-including atomic orbital NMR chemical shifts calculation, followed by DP4 probability. To understand the pharmacological properties of 17-hydroxycyclooctatin, a network pharmacological approach and molecular docking analyses were used, which also predicted its effects on human breast cancer cell lines. Cytotoxicity and antiestrogenic activity of 17-hydroxycyclooctatin were determined, and it was found this compound may be an ERα antagonist.

Glutamate neurotoxicity has been implicated in neuronal death in both acute CNS injury and in chronic neurodegenerative diseases. Five unique cyclic depsipeptides with neuroprotective activity, colletotrichamides A–E (1–5), were isolated from cultures of a halophyte Suaeda japonica-associated fungus, Colletotrichum gloeosporioidesJS419. Spectroscopic analysis revealed that they were glycosylated cyclic lipodepsipeptides. Their relative configurations were determined by ROESY and J-based configuration analysis, and absolute configurations were established by chemical reactions including modified Mosher’s method, advanced Marfey’s method, and sugar derivatization. This is the first report of a glycosylated dimethyl-trioxygenated dodecanoyl moiety, and the relative as well as absolute stereochemistry was elucidated herein for the first time. Colletotrichamide C exhibited strong neuroprotective activity against glutamate in hippocampal HT22 cells.

The objective of our study was to analyze the neuroprotective effects of ginsenoside derivatives Rb1, Rb2, Rc, Rd, Rg1, and Rg3 against glutamate-mediated neurotoxicity in HT22 hippocampal mouse neuron cells.

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.

Many hangover cure products containing natural ingredients that are also effective against alcohol-related liver damage or improve liver function have recently become available. In addition to curing liver damage, antioxidants, anti-inflammatory agents, and blood ethanol reduction aids are emerging as relief targets that reduce hangover symptoms. We investigated the ameliorating effect of WON-21 herbal medicinal products by studying the mixing ratio of oriental medicine concept with respect to antioxidant potential, anti-inflammation, and aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH) enzyme activities. WON-21 and its components exerted antioxidant and anti-inflammatory effects. Rutin, taxifolin, and quercetin showed superior antioxidant effects compared to the other components. WON-12 effectively reduced iNOS and COX-2 in LPS-stimulated macrophages. Quercetin and apigenin were 2 compounds effective for the inhibition of iNOS and COX-2. WON-21 and quercetin also significantly increased the activities of ALDH and ADH enzymes in a concentration-dependent manner.

Dangkwisoo-san (DS) is a traditional Korean herbal medicine used to treat traumatic diseases, including pulmonary contusions, traumatic pneumothorax, bruising, and ankle sprain. Quality control (QC) biomarkers for DS can help ensure its safety and efficacy. Although chemical quality assessments are performed to ensure consistent efficacy of DS, the identity and quantity of the compounds contained within a given natural product is a frequent complication. We conducted a literature review to identify biological assays that support the chemical QC of DS. The results of our investigation confirmed that in vitro experiments with aqueous and alcoholic extracts of DS exhibited positive effects on many aspects of treatment. With 80% EtOH extraction, a low concentration of DS (1 μg/ml) significantly diminished the expression of inflammatory factors, such as nitric oxide (NO), TNF-α, IL-1β, and IL-6, in the Raw264.7 cell line. MeOH extracts activated NRF2 and antioxidant activities in response to the inflammatory inducer LPS, and water extracts of DS remarkably reduced proinflammatory cytokine levels compared to dexamethasone and cyclosporin treatments. Aqueous extracts of DS at a moderate dose of 125 μg/ml supported bone regeneration, recovered ischemic injury in an eNOS-dependent manner, and prevented metabolic disorders (TRPM7 channel inhibition). Cytokines, NO, and immunoglobulins are potential biological QC biomarkers to assess the anti-inflammation and immune response to DS. Future quality evaluation studies of herbal medicines (herbal prescriptions) should aim to select the mechanism-based in vitro efficacy evaluation methods that can estimate consistent clinical effects.

Anorexia means loss of appetite and is a state whereby a desire to eat is either reduced or eliminated resulting in reducing or stopping food intake. Sipjeondaebo-tang (SDT) and Hyangsayukgunja-tang (HYT) are prescriptions known to have appetite-improving effects, but studies on their mechanisms and active components are insufficient. The hypothalamus is the center of appetite control, and various appetite control mechanisms are known. We used mouse hypothalamic neuronal GT1-7 cells as appetite control center cells and analyzed the difference in efficacy between SDT and HYT using microarray and network pharmacology. Microarray analysis showed that SDT and HYT affect the regulation of genes related to appetite control in the digestive tract and central nervous system. Using network pharmacology, we analyzed the differential expression of neuropeptide Y receptors, glucagon, corticotropin-releasing hormone receptors 1, and 5-hydroxytryptamine receptor 4 among the 17 anorexia-related genes selected from the comparative toxicogenomics database and also analyzed the active components that affect gene expression. In conclusion, the appetite-related genes contributed to anorexia control, and the difference in the action mechanism of the two complex prescriptions could be explained.

Roots of Glehnia littoralishave been used to heal stroke as a traditional medicine. Even though many studies on this plant have been conducted, the secondary metabolites produced by its endophytes and their bioactivities have not been investigated thus far. Therefore, a new meroditerpenoid named sartorypyrone E (1) and eight known compounds (2–9) were isolated from extracts of cultured Neosartorya fischeriJS0553, an endophyte of G. littoralis. The isolated metabolites were identified using spectroscopic methods and chemical reaction, based on a comparison to literature data. Relative and absolute stereochemistries of compound 1were also elucidated. To identify the protective effects of isolated compounds (1–9) in HT22 cells against glutamate-induced cytotoxicity, we assessed inhibition of cell death, intracellular reactive oxygen species (ROS) accumulation, and calcium ion (Ca2+) influx. Among the isolates, compound 8, identified as fischerin, showed significant neuroprotective activity on glutamate-mediated HT22 cell death through inhibition of ROS, Ca2+influx, and phosphorylation of mitogen-activated protein kinase, including c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38. The results suggested that the metabolites produced by the endophyte N. fischeriJS0553 might be related to the neuroprotective activity of its host plant, G. littoralis.

Fermented black ginseng (FBG) is produced through several cycles of steam treatment of raw ginseng, at which point its color turns black. During this process, the original ginsenoside components of raw ginseng (e.g., Re, Rg1, Rb1, Rc, and Rb2) are altered, and less-polar ginsenosides are generated (e.g., Rg3, Rg5, Rk1, and Rh4). The aim of this study was to determine the effect of FBG on wound healing.

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 ginsengand its components in preventing neurodegeneration has increased significantly in the past decade. The beneficial effects of P. ginsengon 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. ginsengand its components in the treatment and prevention of neurodegenerative diseases.

Colletotrichumsp. JS-0367 was isolated from Morus alba(mulberry), identified, and cultured on a large scale for chemical investigation. One new anthraquinone (1) and three known anthraquinones (2–4) were isolated and identified using spectroscopic methods including 1D/2D-NMR and HRESIMS. Although the neuroprotective effects of some anthraquinones have been reported, the biological activities of the four anthraquinones isolated in this study have not been reported. Therefore, the neuroprotective effects of these compounds were determined against murine hippocampal HT22 cell death induced by glutamate. Compound 4, evariquinone, showed strong protective effects against HT22 cell death induced by glutamate by the inhibition of intracellular ROS accumulation and Ca2+influx triggered by glutamate. Immunoblot analysis revealed that compound 4reduced the phosphorylation of MAPKs (JNK, ERK1/2, and p38) induced by glutamate. Furthermore, compound 4strongly attenuated glutamate-mediated apoptotic cell death.

The aim of the present study was to evaluate the potential protective effects of six ginsenosides (Rb1, Rb2, Rc, Rd, Rg1, and Rg3) isolated from Panax ginsengagainst tacrolimus (FK506)-induced apoptosis in renal proximal tubular LLC-PK1 cells.

Panax ginsenghas been used since ancient times based on the traditional Asian medicine theory and clinical experiences, and currently, is one of the most popular herbs in the world. To date, most of the studies concerning P. ginsenghave focused on specific mechanisms of action of individual constituents. However, in spite of many studies on the molecular mechanisms of P. ginseng, it still remains unclear how multiple active ingredients of P. ginsenginteract with multiple targets simultaneously, giving the multidimensional effects on various conditions and diseases. In order to decipher the systems-level mechanism of multiple ingredients of P. ginseng, a novel approach is needed beyond conventional reductive analysis. We aim to review the systems-level mechanism of P. ginsengby adopting novel analytical framework–network pharmacology. Here, we constructed a compound-target network of P. ginsengusing experimentally validated and machine learning-based prediction results. The targets of the network were analyzed in terms of related biological process, pathways, and diseases. The majority of targets were found to be related with primary metabolic process, signal transduction, nitrogen compound metabolic process, blood circulation, immune system process, cell-cell signaling, biosynthetic process, and neurological system process. In pathway enrichment analysis of targets, mainly the terms related with neural activity showed significant enrichment and formed a cluster. Finally, relative degrees analysis for the target-disease association of P. ginsengrevealed several categories of related diseases, including respiratory, psychiatric, and cardiovascular diseases.

Phytoestrogens are naturally occurring plant‐derived chemicals that exert female hormone‐like activities similar to those of endogenous estrogens. The purpose of this study was to quantitate the estrogenic activity of six chemical constituents (apigenin, hispidulin, cirsimaritin, cirsimarin, pectolinarin, and linarin) of Cirsium japonicumvar. maackiiusing several in vitroassays. Reporter gene activation by each compound was examined using a human breast cancer (MCF‐7) cell‐based transactivation assay. Proliferative activity was also examined using MCF‐7 cells. Reporter gene activation in MCF‐7 cells by cirsimaritin was significantly suppressed by co‐administration of the estrogen receptor (ER) antagonist ICI 182,780, indicating that cirsimaritin is an ER agonist. Under experimental conditions simulating postmenopausal syndrome (i.e., a low concentration of estrogen), cirsimaritin exerted beneficial effects on MCF‐7 cells by increasing estrogenic activity. These results suggest that cirsimaritin is an effective estrogenic compound that can improve postmenopausal symptoms.

The attack of reactive oxygen species (ROS) on unsaturated fatty acids causes peroxidation. The membranes of liver cells are rich in unsaturated fatty acids, which are a target of lipid peroxidation by free radicals. The purpose of the present study was to identify the hepatoprotective potential of Lonicera caeruleaand its active compound, cyanidin 3‐O‐glucoside, on tertiary butyl hydroperoxide (tBHP)‐induced oxidative damage in HepG2cells. L. caeruleaextract and its active compound, cyanidin 3‐O‐glucoside, showed a dose‐dependent hepatoprotective effect on tBHP‐induced HepG2cell damage. In addition, L. caeruleaand cyanidin 3‐O‐glucoside inhibited the production of intracellular ROSin tBHP‐treated HepG2cells. The protein expression of phosphorylated‐extracellular signal‐regulated kinases and Akt, which are responsible for cell protection against ROS, were increased after treatment with cyanidin 3‐O‐glucoside (50 and 100 μM) in a dose‐dependent manner. Therefore, cyanidin 3‐O‐glucoside is the active compound in L. caerulea, which is responsible for the hepatoprotective effects through the inhibition of ROSand the activation of antioxidant mechanisms.

Heat-processed ginseng, sun ginseng (SG), has been reported to have improved therapeutic properties compared with raw forms, such as increased antidiabetic, anti-inflammatory, and antihyperglycemic effects. The aim of this study was to investigate the antiobesity effects of SG through the suppression of cell differentiation and proliferation of mouse 3T3-L1 preadipocyte cells and the lipid accumulation in Caenorhabditis elegans.

Compound FK506 is an immunosuppressant agent that is frequently used to prevent rejection of solid organs upon transplant. However, nephrotoxicity due to apoptosis and inflammatory response mediated by FK506 limit its usefulness. In this study, the protective effect of Korean Red Ginseng (KRG) against FK506-induced damage in LLC-PK1 pig kidney epithelial cells was investigated.

Fermented black ginseng (FBG) is processed ginseng by the repeated heat treatment and fermentation of raw ginseng. The protective effect and mechanism of FBG on cisplatin-induced nephrotoxicity was investigated to evaluate its therapeutic potential.

Ginsenosides are active components of Panax ginsengthat exert various health benefits including kidney protection effect. The medicinal activity of ginsenosides can be enhanced by modulating their stereospecificity by heat processing. Ginsenosides Rk2 and Rh3 represent positional isomers of the double bond at C-20(21) or C-20(22).

Three new isoflavonoid glycosides, termisoflavones A–C (1–3), and eight isoflavonoids (4–11) were isolated from termite-associated Streptomycessp. RB1 recovered from the cuticle of the South African termite, Macrotermes natalensis. The structures of new compounds were determined by spectroscopic methods including 1D and 2D NMR and HR-MS analysis, as well as comparison of their NMR data with those of related isoflavonoid glycoside derivatives. The absolute configurations of the sugar moieties were clarified by chemical reactions. None of the isolates (1–11) displayed antifungal or antimicrobial activities (MICs > 100 µg/mL), whereas compounds 6and 11ameliorated cisplatin-induced kidney cell damage to 80% of the control value at a cisplatin dose of 25 µM.