Mass spectrometry-guided isolation of thiodiketopiperazines from an EtOAc-extract of Setosphaeria rostrata culture medium and their anti-skin aging effects on TNF-α-induced human dermal fibroblasts.

Using mass spectrometry (MS)-guided isolation methods, a new thiodiketopiperazine derivative (1) and exserohilone (2) were isolated from an EtOAc-extract of Setosphaeria rostrata culture medium. The chemical structure of the new compound was elucidated by MS and NMR spectroscopy, and the absolute configurations were established by the quantum mechanical calculations of electronic circular dichroism. All isolated compounds were examined for their effects on reactive oxygen species (ROS) production, matrix metalloproteinase 1 (MMP-1) secretion, and procollagen type I α1 secretion in tumor necrosis factor (TNF)-α-induced human dermal fibroblasts. Compound 1 and exserohilone (2) exhibited the inhibition of TNF-α-induced ROS generation and MMP-1 secretion. Additionally, compound 1 and exserohilone (2) increased the procollagen type I α1 secretion. Compound 1 docked computationally into the active site of MMP-1 (-6.0 kcal/mol).

Chemical Constituents from the Roots of Angelica reflexa That Improve Glucose-Stimulated Insulin Secretion by Regulating Pancreatic ß-Cell Metabolism.

The aim of this study was to discover bioactive constituents of Angelica reflexa that improve glucose-stimulated insulin secretion (GSIS) in pancreatic ß-cells. Herein, three new compounds, namely, koseonolin A (1), koseonolin B (2), and isohydroxylomatin (3), along with 28 compounds (4-31) were isolated from the roots of A. reflexa by chromatographic methods. The chemical structures of new compounds (1-3) were elucidated through spectroscopic/spectrometric methods such as NMR and HRESIMS. In particular, the absolute configuration of the new compounds (1 and 3) was performed by electronic circular dichroism (ECD) studies. The effects of the root extract of A. reflexa (KH2E) and isolated compounds (1-31) on GSIS were detected by GSIS assay, ADP/ATP ratio assay, and Western blot assay. We observed that KH2E enhanced GSIS. Among the compounds 1-31, isohydroxylomatin (3), (-)-marmesin (17), and marmesinin (19) increased GSIS. In particular, marmesinin (19) was the most effective; this effect was superior to treatment with gliclazide. GSI values were: 13.21 ± 0.12 and 7.02 ± 0.32 for marmesinin (19) and gliclazide at a same concentration of 10 µM, respectively. Gliclazide is often performed in patients with type 2 diabetes (T2D). KH2E and marmesinin (19) enhanced the protein expressions associated with pancreatic ß-cell metabolism such as peroxisome proliferator-activated receptor γ, pancreatic and duodenal homeobox 1, and insulin receptor substrate-2. The effect of marmesinin (19) on GSIS was improved by an L-type Ca2+ channel agonist and K+ channel blocker and was inhibited by an L-type Ca2+ channel blocker and K+ channel activator. Marmesinin (19) may improve hyperglycemia by enhancing GSIS in pancreatic ß-cells. Thus, marmesinin (19) may have potential use in developing novel anti-T2D therapy. These findings promote the potential application of marmesinin (19) toward the management of hyperglycemia in T2D.

New Sesquiterpene Glycosides from the Flowers of Aster koraiensis and Their Inhibition Activities on EGF- and TPA-Induced Cell Transformation.

In total, four new eudesmane-type sesquiterpene glycosides, askoseosides A-D (1-4), and 18 known compounds (5-22) were isolated from the flowers of Aster koraiensis via chromatographic techniques. Chemical structures of the isolated compounds were identified by spectroscopic/spectrometric methods, including NMR and HRESIMS, and the absolute configuration of the new compounds (1 and 2) was performed by electronic circular dichroism (ECD) studies. Further, the anticancer activities of the isolated compounds (1-22) were evaluated using the epidermal growth factor (EGF)-induced as well as the 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced cell transformation assay. Among the 22 compounds, compounds 4, 9, 11, 13-15, 17, 18, and 22 significantly inhibited both EGF- and TPA-induced colony growth. In particular, askoseoside D (4, EGF: 57.8%; TPA: 67.1%), apigenin (9, EGF: 88.6%; TPA: 80.2%), apigenin-7-O-ß-d-glucuronopyranoside (14, EGF: 79.2%; TPA: 70.7%), and 1-(3',4'-dihydroxycinnamoyl) cyclopentane-2,3-diol (22, EGF: 60.0%; TPA: 72.1%) showed higher potent activities.

Neuroprotective effect of Geijigadaehwang-tang against trimethyltin-induced hippocampal neurodegeneration: An in vitro and in vivo study.

ETHNOPHARMACOLOGICAL RELEVANCE: Patients with dementia are diagnosed with deficiency patterns and interior patterns in traditional Chinese medicine due to decreased physical strength, mental atrophy including cognitive function, and decreased motor function in the gastrointestinal tract. Since "greater yin symptom" in Shanghanlun has been interpreted as interior, deficiency, and cold pattern in traditional Chinese medicine, it is necessary to determine whether Geijigadaehwang-tang (GDT) has therapeutic effects on neurodegenerative diseases and the underlying mechanism if it has such effects. AIMS OF THE STUDY: Trimethyltin (TMT), a neurotoxic organotin compound, has been used to induce several neurodegenerative diseases, including epilepsy and Alzheimer's disease. This study aimed to evaluate the therapeutic efficacy of GDT for TMT-induced hippocampal neurodegeneration and seizures and to determine the mechanisms involved at the molecular level. MATERIALS AND METHODS: The main components of GDT were analyzed using ultra-performance liquid chromatography. TMT was used to induce neurotoxicity in microglial BV-2 cells and C57BL6 mice. GDT was administered at various doses to determine its neuroprotective and seizure inhibition effects. The inhibitory effects of GDT on TMT-induced apoptosis, inflammatory pathways, and oxidative stress pathways were determined in the mouse hippocampal tissues. RESULTS: GDT contained emodin, chrysophanol, albiflorin, paeoniflorin, 6-gingerol, and liquiritin apioside. In microglial BV-2 cells treated with TMT, GDT showed dose-dependent neuroprotective effects. Oral administration of GDT five times for 2.5 days before and after TMT injection inhibited seizures at doses of 180 and 540 mg/kg and inhibited neuronal death in the hippocampus. In hippocampal tissues extracted from mice, GDT inhibited the protein expression of ionized calcium binding adaptor molecule 1, glial fibrillary acidic protein, nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3, and phosphorylated nuclear factor (NF)-κB/total-NFκB ratio. Additionally, GDT inhibited the messenger RNA levels of tumor necrosis factor-α, inducible nitric oxide synthase, apoptosis-associated speck-like protein containing a caspase recruitment domain, caspase-1, interleukin-1ß, nuclear factor erythroid-2-related factor 2, and heme oxygenase-1. CONCLUSION: This study's results imply that GDT might have neuroprotective potential in neurodegenerative diseases through neuronal death inhibition and anti-inflammatory and antioxidant mechanisms.

Gekko gecko extract attenuates airway inflammation and mucus hypersecretion in a murine model of ovalbumin-induced asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Gekko gecko is used as a traditional medicine for various diseases including respiratory disorders in northeast Asian countries, mainly Korea, Japan, and China. AIM OF THE STUDY: Allergic asthma is a chronic respiratory disease caused by an inappropriate immune response. Due to the recent spread of coronavirus disease 2019, interest in the treatment of pulmonary disorders has rapidly increased. In this study, we investigated the anti-asthmatic effects of G. gecko extract (GGE) using an established mouse model of ovalbumin-induced asthma. MATERIALS AND METHODS: To evaluate the anti-asthmatic effects of GGE, we evaluated histological changes and the responses of inflammatory mediators related to allergic airway inflammation. Furthermore, we investigated the regulatory effects of GGE on type 2 helper T (Th2) cell activation. RESULTS: Administration of GGE attenuated asthmatic phenotypes, including inflammatory cell infiltration, mucus production, and expression of Th2 cytokines. Furthermore, GGE treatment reduced Th2 cell activation and differentiation. CONCLUSIONS: These results indicate that GGE alleviates allergic airway inflammation by regulating Th2 cell activation and differentiation.

Clerodane Diterpenoids Identified from Polyalthia longifolia Showing Antifungal Activity against Plant Pathogens.

In the search for new natural resources showing plant disease control effects, we found that the methanol extract of Polyalthia longifolia suppressed fungal disease development in plants. To identify the bioactive substances, the methanol extract of P. longifolia was extracted by organic solvents, and consequently, four new 2-oxo-clerodane diterpenes (1-4), a new 4(3 → 2)-abeo-clerodane diterpene (5), together with ten known compounds (6-16) were isolated and identified from the extracts. Of the new compounds, compound 2 showed a broad spectrum of antifungal activity with moderated minimum inhibitory concentration (MIC) values in a range of 50-100 µg/mL against tested fungal pathogens. Considering with the known compounds, compound 6 showed the most potent antifungal activity with an MIC value in the range of 6.3-12.5 µg/mL. When compound 6 was evaluated for an in vivo antifungal activity against rice blast, tomato late blight, and pepper anthracnose, compound 6 reduced the plant disease by at least 60% compared to the untreated control at concentrations of 250 and 500 µg/mL. Together, our results suggested that the methanol extract of twigs and leaves of P. longifolia and its major compound 6 could be used as a source for the development of eco-friendly plant protection agents.

Phenolic constituents isolated from Senna tora sprouts and their neuroprotective effects against glutamate-induced oxidative stress in HT22 and R28 cells.

The consumption of sprouts has been steadily increasing due to their being an excellent source of nutrition. It is known that the bioactive constituents of legumes can be increased after germination. In this study, the extract from Senna tora sprouts is shown to exhibit improved radical scavenging activities and better neuroprotective effects in HT22 hippocampal neuronal (HT22) and R28 retina precursor (R28) cells than those from seeds due to an increased content of phenolic constituents, especially compounds 1 and 3-6. A phytochemical investigation of S. tora sprouts resulted in the isolation of two new naphthopyrone glycosides (1-2) with 27 previously reported compounds. Their structures were determined via interpreting spectroscopic data. Compounds 1 and 3-6 were found to possess radical scavenging activities and neuroprotective effects against oxidative stress in both neuronal cells. Hence, Senna tora sprouts and their constituents may be developed as natural neuroprotective agents via antioxidative effects.

Anti-inflammatory spiroditerpenoids from Penicillium bialowiezense.

Inflammation is a vital process that maintains tissue homeostasis. However, it is widely known that uncontrolled inflammation can contribute to the development of various diseases. This study aimed to discover anti-inflammatory metabolites from Penicillium bialowiezense. Seven spiroditerpenoids, including two new compounds, breviones P and Q (1 and 2), were isolated and characterized by various spectroscopic and spectrometric methods. All isolated compounds were initially tested for their inhibitory effects against lipopolysaccharide-induced nitric oxide (NO) production in RAW 264.7 macrophages. Of these, brevione A (3) exhibited this activity with a half-maximal inhibitory concentration value of 9.5 µM. Further mechanistic studies demonstrated that 3 could suppress the expression of pro-inflammatory cytokines and mediators, such as NO, prostaglandin E2, interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, and IL-12 by inhibiting the activation of nuclear factor-kappa B and c-Jun N-terminal kinase.

Chemical constituents from basidiomycete Basidioradulum radula culture medium and their cytotoxic effect on human prostate cancer DU-145 cells.

Eight new naphtho[1,2-c]furan derivatives (1-8) along with six known analogues (9-14) were isolated from culture medium of the basidiomycete Basidioradulum radula. The structures of these compounds were identified using spectroscopic analysis, and their absolute configurations were resolved using X-ray diffraction, ECD, and VCD. Compounds 7 and 14 inhibited the cell viability of human prostate cancer DU-145 cells with IC50 values of 7.54 ± 0.03 µM and 5.04 ± 0.03 µM, respectively. At 8 µM, compounds 7 and 14 increased the percentage of apoptotic cells and upregulated the protein expression related to the apoptosis caspase pathways in DU-145 cells. Furthermore, the hallmarks of cells undergoing apoptosis, such as chromatin condensation, were also observed at this concentration. However, compound 7 and 14 showed no effect on the proliferation of splenocytes isolated from cyclophosphamide-induce immunosuppressed mice.

Chemical Constituents of the Egg Cases of Tenodera angustipennis (Mantidis ootheca) with Intracellular Reactive Oxygen Species Scavenging Activity.

As a traditional medicine with potential antioxidant effects, Tenodera angustipennis egg cases (Mantidis ootheca) are a potential source of new bioactive substances. Herein, three new N-acetyldopamine derivatives, namely, (+)-tenoderin A (1a), (-)-tenoderin A (1b), and tenoderin B (2), along with thirteen known compounds (3-15), were isolated from a 70% EtOH extract of T. angustipennis egg cases. Compound 1 was isolated as a racemic mixture, and two enantiomers (1a and 1b) were successfully separated by chiral-phase preparative HPLC. The chemical structures of the new compounds were established by NMR spectroscopy and high-resolution electrospray ionization mass spectrometry, and the absolute configurations of enantiomers 1a and 1b were determined by electronic circular dichroism spectroscopy. All the new compounds exhibited antioxidant activities with IC50 values of 19.45-81.98 µM, as evaluated using free-radical scavenging assays, with the highest activity observed for compound 2. In addition, compounds 1a, 1b, and 2 exhibited inhibitory activities on intracellular reactive oxygen species generation.

Cicadidae Periostracum Attenuates Atopic Dermatitis Symptoms and Pathology via the Regulation of NLRP3 Inflammasome Activation.

Atopic dermatitis (AD) is a multifactorial inflammatory skin disease of complex etiology. Despite its increasing prevalence, treatment for AD is still limited. Crude drugs, including herbal extracts or natural resources, are being used to treat AD symptoms, with minimum side effects. Cicadidae Periostracum (CP), derived from the slough of insects belonging to the family Cicadidae, is a commonly used crude drug in traditional Asian medicine to treat/control epilepsy, shock, and edema. However, the effect of CP on AD-like skin lesions is unknown. In this study, we examined the effect of a CP water extract on AD disease development in vivo, using a house dust mite-induced AD mouse model, and in vitro, using HaCaT keratinocytes and a 3D human skin equivalent system. Importantly, CP administration alleviated house dust mite-induced AD-like symptoms, suggested by the quantified dermatitis scores, animal scratching behaviors, skin moisture retention capacity, and skin lesion and ear thickness. Furthermore, histopathological analysis demonstrated that CP decreased intralesional mast cell infiltration. In addition, CP treatments decreased the systemic levels of immunoglobulin E, histamine, and thymic stromal lymphopoietin (TSLP) and the local mRNA expression of TSLP and several Th1/Th2 cytokines. Our data suggest that these effects were mediated by the inhibition of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation. In vivo and in vitro CP treatments resulted in the downregulation of inflammasome components, such as ASC and cleaved caspase-1, as well as related mediators such as IL-1ß and reactive oxygen species. Collectively, our results suggest that CP is a potential therapeutic agent for AD, controlling inflammatory responses through the suppression of NLRP3 inflammasome activation.

Pharmacological Effects of Agastache rugosa against Gastritis Using a Network Pharmacology Approach.

Agastache rugosa is used as a Korean traditional medicine to treat gastric diseases. However, the active ingredients and pharmacological targets of A. rugosa are unknown. In this study, we aimed to reveal the pharmacological effects of A. rugosa on gastritis by combining a mice model and a network pharmacology method. The macrophage and gastritis-induced models were used to evaluate the pharmacological effects of A. rugosa. The results show that A. rugosa relieved mucosal damage induced by HCl/EtOH in vivo. Network analysis identified 99 components in A. rugosa; six components were selected through systematic screening, and five components were linked to 45 gastritis-related genes. The main components were acacetin and luteolin, and the identified core genes were AKT serine/threonine kinase 1 (AKT1), nuclear factor kappa B inhibitor alpha (NFKBIA), and mitogen-activated protein kinase-3 (MAPK3) etc. in this network. The network of components, target genes, protein-protein interactions, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was closely connected with chemokines and with phosphoinositide 3-kinase-Akt (PI3K/AKT), tumor-necrosis-factor alpha (TNFα), mitogen-activated protein kinase, nuclear factor kappa B, and Toll-like receptor (TLR) pathways. In conclusion, A. rugosa exerts gastro-protective effects through a multi-compound and multi-pathway regulatory network and holds potential for treating inflammatory gastric diseases.

Chemical Constituents from the Aerial Parts of Elsholtzia ciliata and Their Protective Activities on Glutamate-Induced HT22 Cell Death.

A new phenolic glucoside, (7E,9E)-3-hydroxyavenalumic acid-3-O-[6'-O-(E)-caffeoyl]-ß-d-glucopyranoside (1), and three new acetylated flavone glycosides, acacetin-7-O-[ß-d-glucopyranosyl(1″″→2″)-4‴-O-acetyl-α-l-rhamnopyranosyl(1‴→6″)]-ß-d-glucopyranoside (3), acacetin-7-O-[6″″-O-acetyl-ß-d-glucopyranosyl(1″″→2″)-3‴-O-acetyl-α-l-rhamnopyranosyl(1‴→6″)]-ß-d-glucopyranoside (5), and acacetin-7-O-[3″″,6″″-di-O-acetyl-ß-d-glucopyranosyl(1″″→2″)-4‴-O-acetyl-α-l-rhamnopyranosyl(1‴→6″)]-ß-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 1 and 3, exhibited neuroprotective effects against glutamate-induced HT22 cell death. In particular, compounds 2, 16, 17, 20, 22, 28, 29, and 31 presented potent neuroprotective effects with EC50 values of 1.5-8.3 µM.

Anti-inflammatory Metabolites from Chaetomium nigricolor.

Twelve metabolites were obtained from the culture media of Chaetomium nigricolor, including a new furan derivative, methyl succinyl Sumiki's acid (1), and two new atropisomers of the previously reported bis-naphtho-γ-pyrones, (aS)-asperpyrone A and (aS)-fonsecinone A (2 and 3). The structures were elucidated by spectroscopic, chemical, and chiroptical techniques. Compounds 2 and 3 inhibited nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 macrophages. Compound 2 was found to inhibit nuclear factor-kappa B and c-Jun N-terminal kinase activation, in turn suppressing pro-inflammatory mediators and cytokines including nitric oxide, prostaglandin E2, interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, and IL-12.

Therapeutic Effects of Licorice and Dried Ginger Decoction on Activity-Based Anorexia in BALB/c AnNCrl Mice.

Licorice and dried ginger decoction (Gancao-ganjiang-tang, LGD) is used for nausea and anorexia, accompanied by excessive sweating in Traditional Chinese Medicine. Herein, we investigated the therapeutic effects of LGD using the activity-based anorexia (ABA) in a mouse model. Six-week-old female BALB/c AnNCrl mice were orally administered LGD, water, licorice decoction, dried ginger decoction, or chronic olanzapine, and their survival, body weight, food intake, and wheel activity were compared in ABA. Additionally, dopamine concentration in brain tissues was evaluated. LGD significantly reduced the number of ABA mice reaching the drop-out criterion of fatal body weight loss. However, LGD showed no significant effects on food intake and wheel activity. We found that in the LGD group the rise of the light phase activity rate inhibited body weight loss. Licorice or dried ginger alone did not improve survival rates, they only showed longer survival periods than chronic olanzapine when combined. In addition, LGD increased the dopamine concentration in the brain. The results from the present study showed that LGD improves the survival of ABA mice and its mechanism of action might be related to the alteration of dopamine concentration in the brain.

Chemical Constituents of the Leaves of Butterbur (Petasites japonicus) and Their Anti-Inflammatory Effects.

Two new aryltetralin lactone lignans, petasitesins A and B were isolated from the hot water extract of the leaves of butterbur (Petasites japonicus) along with six known compounds. The chemical structures of lignans 1 and 2 were elucidated on the basis of 1D and 2D nuclear magnetic resonance (NMR) spectroscopic data, electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectra. Petasitesin A and cimicifugic acid D showed significant inhibitory effects on the production of both prostaglandin E2 (PGE2) and NO in RAW264.7 macrophages. The expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were inhibited by compound 1 in RAW264.7 cells. Furthermore, compounds 1 and 3 exhibited strong affinities with both iNOS and COX-2 enzymes in molecular docking studies.

Batryticatus Bombyx Protects Dopaminergic Neurons Against MPTP-Induced Neurotoxicity by Inhibiting Oxidative Damage.

Oxidative stress plays an important role in the degeneration of dopaminergic neurons in Parkinson's disease (PD). Altered redox homeostasis in neurons interferes with several biological processes, ultimately leading to neuronal death. Oxidative damage has been identified as one of the principal mechanisms underlying the progression of PD. Several studies highlight the key role of superoxide radicals in inducing neuronal toxicity. Batryticatus Bombyx (BB), the dried larva of Bombyx mori L. infected by Beauveria bassiana (Bals.) Vuill., has been used in traditional medicine for its various pharmacological effects. In the present study, BB showed a beneficial effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity by directly targeting dopaminergic neurons. Treatment with BB improved behavioral impairments, protected dopaminergic neurons, and maintained dopamine levels in PD mouse models. Here, we investigated the protective effects of BB on MPTP-induced PD in mice and explored the underlying mechanisms of action, focusing on oxidative signaling. In MPTP-induced PD, BB promoted recovery from impaired movement, prevented dopamine depletion, and protected against dopaminergic neuronal degradation in the substantia nigra pars compacta (SNpc) or the striatum (ST). Moreover, BB upregulated mediators of antioxidative response such as superoxidase dismutase (SOD), catalase (CAT), glutathione (GSH), Heme oxygenase 1 (HO-1), and NAD(P)H (nicotinamide adenine dinucleotide phosphate) dehydrogenase (NQO1). Thus, treatment with BB reduced the oxidative stress, improved behavioral impairments, and protected against dopamine depletion in MPTP-induced toxicity.

Cicadidae Periostracum, the Cast-Off Skin of Cicada, Protects Dopaminergic Neurons in a Model of Parkinson's Disease.

Parkinson's disease (PD) is characterized by dopaminergic neuronal loss in the substantia nigra pars compacta (SNPC) and the striatum. Nuclear receptor-related 1 protein (Nurr1) is a nuclear hormone receptor implicated in limiting mitochondrial dysfunction, apoptosis, and inflammation in the central nervous system and protecting dopaminergic neurons and a promising therapeutic target for PD. Cicadidae Periostracum (CP), the cast-off skin of Cryptotympana pustulata Fabricius, has been used in traditional medicine for its many clinical pharmacological effects, including the treatment of psychological symptoms in PD. However, scientific evidence for the use of CP in neurodegenerative diseases, including PD, is lacking. Here, we investigated the protective effects of CP on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine- (MPTP-) induced PD in mice and explored the underlying mechanisms of action, focusing on Nurr1. CP increased the expression levels of Nurr1, tyrosine hydroxylase, DOPA decarboxylase, dopamine transporter, and vesicular monoamine transporter 2 via extracellular signal-regulated kinase phosphorylation in differentiated PC12 cells and the mouse SNPC. In MPTP-induced PD, CP promoted recovery from movement impairments. CP prevented dopamine depletion and protected against dopaminergic neuronal degradation via mitochondria-mediated apoptotic proteins such as B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X, cytochrome c, and cleaved caspase-9 and caspase-3 by inhibiting MPTP-induced neuroinflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase 2, and glial/microglial activation. Moreover, CP inhibited lipopolysaccharide-induced neuroinflammatory cytokines and response levels and glial/microglial activation in BV2 microglia and the mouse brain. Our findings suggest that CP might contribute to neuroprotective signaling by regulating neurotrophic factors primarily via Nurr1 signaling, neuroinflammation, and mitochondria-mediated apoptosis.

Xylodon flaviporus-Derived Drimane Sesquiterpenoids That Inhibit Osteoclast Differentiation.

The presence of excessive osteoclasts is a major factor in skeletal diseases. The present study aimed to discover osteoclast differentiation inhibitors from the basidiomycete Xylodon flaviporus. Seven new drimane sesquiterpenoids (1-7) and 7-ketoisodrimenin-5-ene (8) were obtained and characterized by various spectroscopic methods. The isolated compounds were evaluated for their inhibitory effects against receptor activator of nuclear factor-kappa-B ligand-induced osteoclastogenesis in mouse bone marrow macrophages. Compounds 1, 3, and 6 showed potent activities with IC50 values of 1.6, 0.9, and 2.1 µM, respectively, while 4, 5, and 7 exhibited relatively weak activities with IC50 values of 10.7, 10.1, and 8.5 µM, respectively.

Furanocoumarins from the Roots of Angelica dahurica with Inhibitory Activity against Intracellular Reactive Oxygen Species Accumulation.

Five new furanocoumarins, dahuribirin H (1), dahuribirin I (2), (2'S)-(+)-5-(2'-hydroxy-3'-methylbut-3'-enyloxy)-8-(3''-methylbut-2″-enyloxy)psoralen (3), (2'R)-(+)-5-(2',3'-epoxy-3'-methylbutoxy)-8-(3″-methylbut-2″-enyloxy)psoralen (4), and 5-methoxy-8-((Z)-4'-(3″-methylbutanoate)-3'-methylbut-2'-enyloxy)psoralen (5), along with 15 known compounds (6-20), were isolated from the roots of Angelica dahurica. The structures of the new compounds were elucidated by spectroscopic analysis, along with electronic circular dichroism calculations and Mosher ester analysis. Compounds 3, 4, 11, 13, and 16 reduced H2O2-induced cell death in HepG2 cells and attenuated reactive oxygen species (ROS) formation without showing cytotoxicity, suggesting that these compounds might have cytoprotective effects against H2O2-induced oxidative damage via ROS scavenging activities.