Gonadal efficacy of Thymus quinquecostatus Celakovski: Regulation of testosterone levels in aging mouse models.

Late-onset hypogonadism (LOH) is an age-related disease in men characterized by decreased testosterone levels with symptoms such as decreased libido, erectile dysfunction, and depression. Thymus quinquecostatus Celakovski (TQC) is a plant used as a volatile oil in traditional medicine, and its bioactive compounds have anti-inflammatory potential. Based on this knowledge, the present study aimed to investigate the effects of TQC extract (TE) on LOH in TM3 Leydig cells and in an in vivo aging mouse model. The aqueous extract of T. quinquecostatus Celakovski (12.5, 25, and 50 µg/mL concentrations) was used to measure parameters such as cell viability, testosterone level, body weight, and gene expression, via in vivo studies. Interestingly, TE increased testosterone levels in TM3 cells in a dose-dependent manner without affecting cell viability. Furthermore, TE significantly increased the expression of genes involved in the cytochrome P450 family (Cyp11a1, Cyp17a1, Cyp19a1, and Srd5a2), which regulate testosterone biosynthesis. In aging mouse models, TE increased testosterone levels without affecting body weight and testicular tissue weight tissue of an aging animal group. In addition, the high-dose TE-treated group (50 mg/kg) showed significantly increased expression of the cytochrome p450 enzymes, similar to the in vitro results. Furthermore, HPLC-MS analysis confirmed the presence of caffeic acid and rosmarinic acid as bioactive compounds in TE. Thus, the results obtained in the present study confirmed that TQC and its bioactive compounds can be used for LOH treatment to enhance testosterone production.

An Integrative Study of Scrophularia takesimensis Nakai in an Ovalbumin-Induced Murine Model of Asthma: The Effect on T Helper 2 Cell Activation.

Scrophularia have traditionally been used as herbal medicines to treat neuritis, sore throats, and laryngitis. In particular, S. takesimensis, a Korean endemic species with restricted distribution on Ulleung Island, holds significant resource and genetic value. However, its pharmacological properties have not been thoroughly evaluated. Thus, we provide detailed morphological characteristics and genomic information for S. takesimensis in this study. Moreover, its pharmacological activity was evaluated in an ovalbumin-induced asthma rat model, using extracts of S. takesimensis roots (100 or 200 mg/kg). The distinguishing features of S. takesimensis from related species include the presence or absence of stem wings, leaf shape, and habitat. The chloroplast (cp) genome of this species is 152,420 bp long and exhibits a conserved quadripartite structure. A total of 114 genes were identified, which included 80 protein-coding genes, 30 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes. The gene order, content, and orientation of the S. takesimensis cp genome was highly conserved and consistent with the general structure observed in S. buergeriana and S. ningpoensis cp genomes. Confirming the anti-inflammatory effects of S. takesimensis extract (STE) using an established mouse model of ovalbumin-induced asthma, we observed reduced asthmatic phenotypes, including inflammatory cell infiltration, mucus production, and suppression of T helper 2 (Th2) cell. Furthermore, STE treatment reduced Th2 cell activation and differentiation. This study underscores the medicinal value of S. takesimensis. The importance of preserving S. takesimensis was revealed and crucial insights were provided for further research on its utilization as a medicinal resource.

Anti-Atopic Effect of Scutellaria baicalensis and Raphanus sativus on Atopic Dermatitis-like Lesions in Mice by Experimental Verification and Compound-Target Prediction.

Scutellaria baicalensis Georgi and Raphanus Sativus Linne herbal mixture (SRE) is a Chinese herbal medicine. In this study, we aimed to evaluate the therapeutic efficacy of SRE as an active ingredient for 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) and to predict the underlying therapeutic mechanisms and involved pathways using network pharmacological analysis. Treatment with SRE accelerated the development of AD-like lesions, improving thickness and edema of the epidermis. Moreover, administering the SRE to AD-like mice suppressed immunoglobulin E and interleukin-4 cytokine and reduced T lymphocyte differentiation. In silico, network analysis was used to predict the exact genes, proteins, and pathways responsible for the therapeutic effect of the SRE against DNCB-induced AD. These results indicated that the SRE exerted protective effects on the DNCB-induced AD-like model by attenuating histopathological changes and suppressing the levels of inflammatory mediators. Therefore, the SRE can potentially be a new remedy for improving AD and other inflammatory diseases and predicting the intracellular signaling pathways and target genes involved. This therapeutic effect of the SRE on AD can be used to treat DNCB-induced AD and its associated symptoms.

Comparative Morphology of Island and Inland Agastache rugosa and Their Gastroprotective Effects in EtOH/HCl-Induced Gastric Mucosal Gastritis.

Agastache rugosa Kuntze (Lamiaceae; Labiatae), a medicinal and functional herb used to treat gastrointestinal diseases, grows well both on islands and inland areas in South Korea. Thus, we aimed to reveal the morphological and micromorphological differences between A. rugosa grown on island and inland areas and their pharmacological effects on gastritis in an animal model by combining morphological and mass spectrophotometric analyses. Morphological analysis showed that island A. rugosa had slightly smaller plants and leaves than inland plants; however, the density of all types of trichomes on the leaves, petioles, and stems of island A. rugosa was significantly higher than that of inland plants. The essential oil component analysis revealed that pulegone levels were substantially higher in island A. rugosa than in inland A. rugosa. Despite the differences between island and inland A. rugosa, treatment with both island and inland A. rugosa reduced gastric damages by more than 40% compared to the gastritis induction group. In addition, expression of inflammatory protein was reduced by about 30% by treatment of island and inland A. rugosa. The present study demonstrates quantitative differences in morphology and volatile components between island and inland plants; significant differences were not observed between the gastritis-inhibitory effects of island and inland A. rugosa, and the efficacy of island A. rugosa was found to be similar to that of A. rugosa grown in inland areas.

Chondroprotective effects of Protaetia brevitarsis seulensis larvae as an edible insect on osteoarthritis in mice.

Osteoarthritis (OA) is a common chronic joint inflammatory disease characterized by progressive destruction of the articular cartilage, bone remodeling, and excessive chronic pain. Most therapeutic approaches do not rescue the progression of OA effectively or provide relief of symptoms. Protaetia brevitarsis seulensis larva (PBSL), which is attracting attention, is an edible insect with very high nutritional value and herbal medicine for the treatment of blood stasis, hepatic disease, and various inflammatory diseases. However, the effect of PBSL on OA has not yet been investigated. This study aimed to demonstrate the effects of PBSL water extract on the progression of OA using monosodium iodoacetate (MIA)-induced mice and SW1353 chondrocytes or murine macrophages. We injected MIA into the intraarticular area of mice following pretreatment with either saline or PBSL (200 mg/kg) for 2 weeks, and then locomotor activity, microcomputed tomography and histopathological analysis, quantitative reverse transcriptase-polymerase chain reaction analysis, and western blot analysis were performed. To determine the molecular effects of PBSL, we used interleukin-1ß (IL-1ß)-induced SW1353 chondrosarcoma or lipopolysaccharide (LPS)-stimulated macrophages. Pretreatment with PBSL diminished the symptoms of OA. Physical activity, articular cartilage damage, and the generation of microfractures were rescued by pretreatment with PBSL in the mouse model. Pretreatment with PBSL suppressed the progress of OA through the regulation of articular cartilage degradation genes and inflammation in both in vivo and in vitro models. Our results demonstrated that PBSL has value as edible insect that can be used in the development of functional foods for OA.

Camellia sinensis (L.) Kuntze Extract Attenuates Ovalbumin-Induced Allergic Asthma by Regulating Airway Inflammation and Mucus Hypersecretion.

Asthma is a pulmonary disease induced by the inhalation of aeroallergens and subsequent inappropriate immune responses. Camellia sinensis (L.) Kuntze has been evaluated as an effective antioxidant supplement produced from bioactive compounds, including flavonoids. In this study, we aimed to determine the effects of Camellia sinensis (L.) Kuntze extract (CE) on ovalbumin-induced allergic asthma. The components of CE were analyzed using high-performance liquid chromatography (HPLC) chromatogram patterns, and asthmatic animal models were induced via ovalbumin treatment. The antioxidant and anti-inflammatory effects of CE were evaluated using 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS), and nitric oxide (NO) assays. Seven compounds were detected in the CE chromatogram. In the ovalbumin-induced mouse model, CE treatment significantly decreased the inflammation index in the lung tissue. CE also significantly decreased eosinophilia and the production of inflammatory cytokines and OVA-specific IgE in animals with asthma. Collectively, our results indicate that CE has anti-inflammatory and antioxidant activities, and that CE treatment suppresses asthmatic progression, including mucin accumulation, inflammation, and OVA-specific IgE production.

Evaluation of Marker Compounds and Biological Activity of In Vitro Regenerated and Commercial Rehmannia glutinosa (Gaertn.) DC. Roots Subjected to Steam Processing.

Rehmannia glutinosa (Gaertn.) DC., belonging to the family Scrophulariaceae, has been known since immemorial times as a prominent oriental drug in East Asia that can treat various ailments, such as kidney disorders, anemia, and diabetes. In order to be applied for medical purposes, R. glutinosa is commonly processed using steam to increase its efficacy and biological activity. The increasing demand for R. glutinosa in the traditional medicine industry encouraged many researchers to develop a fast, efficient, and high-quality production system using biotechnological approaches. This study aimed to compare the chemical and biological activities of in vitro regenerated R. glutinosa (PKR) and commercial R. glutinosa (PCR) samples subjected to steam processing. We assessed the effects of steam processing and the differences in R. glutinosa material on 5-Hydroxymethyl-2-furaldehyde (5-HMF) content, total flavonoid and phenolic content, antioxidant activity, nitric oxide (NO) levels, and anti-inflammatory activity. PKR samples showed a significantly higher content of 5-HMF (0.15%) as compared to PCR samples (0.05%). Compared to unprocessed R. glutinosa (UPR) and PCR samples, PKR again showed the highest total phenolic and flavonoid content of 41.578 mg GAE/g and 17.208 mg RUE/g, respectively. Meanwhile, both processed R. glutinosa samples (PKR and PCR) showed a significantly higher DPPH antioxidant activity ((67.095 + 1.005)% and (61.579 + 0.907)%, respectively) than unprocessed R. glutinosa ((31.452 + 1.371)%). In addition, both PKR and PCR samples showed good anti-inflammatory activity by showing similar effects such as the inhibition of NO production and the suppression of inducible nitric oxide synthase (iNOS). Based on these results, PKR fulfilled the Chinese pharmacopeia standards, in terms of the amount of the marker compounds and showed a high level of bioactivity. Therefore, these findings are expected to be useful in verifying the efficacy of herbal medicines and the availability of suitable materials for medicinal use.

Protective effects of an aqueous extract of Protaetia brevitarsis seulensis larvae against radiation-induced testicular injury in mice.

The larvae of Protaetia brevitarsis seulensis have been used as a food ingredient and are known for their nutritional value and anti-inflammatory properties. However, whether P. brevitarsis seulensis larvae demonstrate protective effects against radiation-induced testicular injury has not been investigated. In this study, the protective effects of an aqueous extract of P. brevitarsis seulensis larvae (PBE) against radiation-induced testicular injury were tested. Male C57BL/6 mice were administered PBE (5 or 10 mg/kg) orally for 14 days before exposure to focal pelvic irradiation. Histopathological examinations were conducted at 8 h and 30 d after radiation exposure. PBE pretreatment reduced the radiation-induced apoptosis of germ cells at 8 h after irradiation and significantly increased testis and epididymis weights relative to those of the irradiated control mice at 30 days. PBE protected against histopathological damage and decreased the radiation-induced effects on the epithelium height and seminiferous tubule diameter. Furthermore, the extract ameliorated the radiation-induced morphological abnormalities of sperm cells and improved their motility. It also prevented a decrease in the epididymal sperm count caused by irradiation. Moreover, the extract alleviated the generation of reactive oxygen species, and its antioxidative activity increased in a dose-dependent manner. Among the six major compounds isolated from PBE, benzoic acid and uridine showed the highest antioxidant activities. These results suggest that PBE protects against radiation-induced testicular injury via its antioxidative properties. Thus, it has potential clinical applicability as a neoadjuvant therapy for the prevention of testicular damage caused by cancer radiotherapy.

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.

Effects of larval extracts from identified Protaetia brevitarsis seulensis against benign prostatic hyperplasia induced by testosterone in rats.

Protaetia brevitarsis seulensis is an animal-based medicine used traditionally in China, Japan, and Korea to treat hepatic disorders; it has been shown to possess various pharmacological effects such as antibacterial and antioxidant activities. In this study, we investigated the effects of P. brevitarsis on a testosterone-induced benign prostatic hyperplasia (BPH) rat model. To establish the BPH model, the animals were administered a subcutaneous injection of testosterone daily for 28 days. P. brevitarsis was administered by oral gavage at doses of 12.5, 25, and 50 mg/kg for 28 days, along with testosterone injection. P. brevitarsis treatment markedly decreased the absolute and relative prostate weight of BPH animals. The levels of dihydrotestosterone was reduced in P. brevitarsis-treated animals compared to those in the BPH animals. Histological analysis of the prostate showed that P. brevitarsis treatment effectively suppressed the testosterone-induced hyperplasia of prostatic epithelial cells, which was accompanied by reductions in the PCNA and Ki-67 expressions in prostatic tissues. These results indicate that P. brevitarsis effectively suppresses testosterone-induced development of BPH, and thus, is a potential therapeutic agent for BPH.

Anti-Inflammation and Protective Effects of Anethum graveolens L. (Dill Seeds) on Esophageal Mucosa Damages in Reflux Esophagitis-Induced Rats.

Anethum graveolens L. (dill seeds) are important medicinal and functional foods in Europe and central and south Asia, often used as a seasoning in daily diets. Anethum graveolens L. seeds (AGS) are used to treat indigestion and have shown physiological activities such as those against hypoglycemia and gastroesophageal disease. This study explored the protective effects of AGS extract on mucosal damages and inflammation in reflux esophagitis rats. AGS inhibited cellular inflammation including NO production and the expression of inflammatory proteins (iNOS and COX2 etc.), cytokines (IL-1ß and TNF-α) and nuclear transfer factor related to NF-κB signaling caused by LPS stimulation in vitro. Furthermore, reflux esophagitis-induced rats were used to observe the anti-inflammatory effect of AGS. Tissue staining and inflammation-related protein expression of rats with acute reflux esophagitis indicated that AGS improved this inflammatory response, such as COX-2 and TNF-α in mucosa. In conclusion, AGS have good physiological activity and the possibility of being used as a medicinal food and a functional resource for the prevention and therapy of gastroesophageal diseases.

Role of Semisulcospira gottschei extract as medicinal food on reflux esophagitis in rats.

Gastroesophageal reflux disease (GERD) is a globally prevalent disease and results from a reflux of gastric contents into the esophagus. Existing synthetic drug-based treatments for GERD have various drawbacks including refractory symptoms, relapse, or resistance due to long-term use or may result in mucosal degeneration, polyps, and osteoporosis. Semisulcospira gottschei (SE), a freshwater snail, has been generally consumed as a food source due to its excellent flavor and nutritional value in Korea and considered to have therapeutic properties for various diseases including dyspepsia, stomachache, and hepatic diseases. The present study aims to investigate whether Semisulcospira gottschei extract (SGE) has a protective effect on reflux esophagitis-induced rat models. The anti-inflammatory effects of SGE were evaluated via NO production in LPS-induced Raw 264.7 macrophage. And the protection effects of SGE were analyzed by assessing the amelioration of mucosal damage and expression of inflammation-associated proteins in reflux esophagitis (RE) rats. Our results indicate that SGE significantly suppressed NO production in LPS-induced raw 264.7 cells without any cytotoxicity. We observed mucosal lesions and histological changes in the esophagus of RE control rats. However, SGE treatment markedly ameliorated mucosal lesion ratio indicated through histological changes. SGE administration suppressed the expression of proteins related to inflammation, such as p-NF-κB, p-IκBα, COX-2, and TNF-α, in esophageal tissue. Moreover, SGE elevated the expression of claudin-5, which is a tight junction protein, involved in barrier function of epithelium and endothelium. The results suggest that SGE is useful as a medicinal food in esophagitis and may be helpful in developing effective treatment protocols for GERD.

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.

Inhibitory effects of Camellia japonica on cell inflammation and acute rat reflux esophagitis.

BACKGROUND: Excessive and continuous inflammation may be the main cause of various immune system diseases. Reflux esophagitis (RE) is a common gastroesophageal reflux disease (GERD). Camellia japonica has high medicinal value and has long been used as a traditional herbal hemostatic medicine in China and Korea. The purpose of this study is to explore the antioxidant and anti-inflammatory activities of CJE and its protective effect on RE. MATERIALS AND METHODS: Buds from C. japonica plants were collected in the mountain area of Jeju, South Korea. Dried C. japonica buds were extracted with 75% ethanol. DPPH and ABTS radical scavenging assay were evaluated according to previous method. The ROS production and anti-inflammatory effects of C. japonica buds ethanol extract (CJE) were evaluated on LPS-induced RAW 264.7 cell inflammation. The protective effects of CJE on RE were conducted in a RE rat model. RESULTS: CJE eliminated over 50% of DPPH and ABTS radical at concentration of 100 and 200 µg/mL, respectively. CJE alleviated changes in cell morphology, reduced production of ROS, NO and IL-1ß. Also, down-regulated expression levels of iNOS, TNF-α, phosphorylated NF-κB, IκBα, and JNK/p38/MAPK. CJE reduced esophageal tissue damage ratio (40.3%) and attenuation of histological changes. In addition, CJE down-regulated the expression levels of TNF-α, IL-1ß, COX-2 and phosphorylation levels of NF-κB and IκBα in esophageal tissue. CONCLUSIONS: CJE possesses good anti-oxidation and anti-inflammatory activity, and can improve RE in rats caused by gastric acid reflux. Therefore, CJE is a natural material with good anti-oxidant and anti-inflammatory activity and has the possibility of being a candidate phytomedicine source for the treatment of RE.

Geranium koreanum, a medicinal plant Geranii Herba, ameliorate the gastric mucosal injury in gastritis-induced mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Geranii Herba, the traditional medicinal plants Korean and northeast China, has been used in the healing of a variety of gastrointestinal inflammation disorders. Geranium koreanum is a congeneric origin plant of Geranii Herba that can be used as medicinal plants with Geranium thunbergii, Geranium sibiricum, Geranium carolinianum, Geranium nepalense, and Geranium japonicam. However, research on the biological activity of Geranium koreanum is currently insufficient. AIM OF THE STUDY: Gastritis is typically characterized by inflammation and irritation, and it is commonly caused by factors such as stress, alcohol consumption, smoking, and the use of anti-inflammatory drugs. In particular, excessive ethanol ingestion is an important cause of gastric disease mediated by mucosal damage by inflammatory cells infiltration. In this study, we investigated whether Geranium koreanum, the well-known traditional medicinal plant, could have a protective effect on gastric mucosal damage in an HCl/EtOH-induced gastritis model by analyzing the inflammation response in gastric tissue. MATERIAL AND METHODS: The cytotoxicity and anti-inflammatory effects of Geranium koreanum were analyzed by determining cell viability and nitric oxide (NO) production, as well as the levels of nuclear factor (NF)-κB proteins in lipopolysaccharide (LPS)-induced cells. Additionally, we measured the damage ratio, conducted histopathological assay by H&E and PAS staining, and determined the levels of pro-inflammation mediator proteins in gastric tissue after induction of gastritis by HCl/EtOH administration in order to analyze the gastro-protective effects of Gerranium koreanum. RESULTS: The ulcer ratio and inflammatory cell infiltration in gastric mucosa were reduced by treatment with Geranium koreanum. Additionally, the expression of inflammatory mediators in gastric tissue was effectively decreased by extracts administrated at 200 mg/kg, as compared to the gastritis control. CONCLUSIONS: We demonstrated that Geranium koreanum could have ameliorating effects against HCl/EtOH-induced gastritis through the anti-inflammatory response, which indicates the potential use of this plant as a natural preventive medicine for gastritis treatment.

Three Scrophularia Species (Scrophularia buergeriana, S. koraiensis, and S. takesimensis) Inhibit RANKL-Induced Osteoclast Differentiation in Bone Marrow-Derived Macrophages.

Scrophulariae Radix, derived from the dried roots of Scrophularia ningpoensis Hemsl. or S. buergeriana Miq, is a traditional herbal medicine used in Asia to treat rheumatism, arthritis, and pharyngalgia. However, the effects of Scrophularia buergeriana, S. koraeinsis, and S. takesimensis on osteoclast formation and bone resorption remain unclear. In this study, we investigated the morphological characteristics and harpagoside content of S. buergeriana, S. koraiensis, and S. takesimensis, and compared the effects of ethanol extracts of these species using nuclear factor (NF)-κB ligand (RANKL)-mediated osteoclast differentiation. The harpagoside content of the three Scrophularia species was analyzed by high-performance liquid chromatography-mass spectrometry (HPLC/MS). Their therapeutic effects were evaluated by tartrate-resistant acid phosphatase (TRAP)-positive cell formation and bone resorption in bone marrow-derived macrophages (BMMs) harvested from ICR mice. We confirmed the presence of harpagoside in the Scrophularia species. The harpagoside content of S. buergeriana, S. koraiensis, and S. takesimensis was 1.94 ± 0.24 mg/g, 6.47 ± 0.02 mg/g, and 5.50 ± 0.02 mg/g, respectively. Treatment of BMMs with extracts of the three Scrophularia species inhibited TRAP-positive cell formation in a dose-dependent manner. The area of hydroxyapatite-absorbed osteoclasts was markedly decreased after treatment with the three Scrophularia species extracts. Our results indicated that the three species of the genus Scrophularia might exert preventive effects on bone disorders by inhibiting osteoclast differentiation and bone resorption, suggesting that these species may have medicinal and functional value.

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.

Ameliorative effects of Magnolia sieboldii buds hexane extract on experimental reflux esophagitis.

Gastroesophageal reflux disease (GERD) is a disease that stomach contents continually refluxing into esophagus causes symptoms and/or complications. The study was working to find natural plant extracts with good effects and small side effects to treat reflux esophagitis (RE). The anti-inflammatory effects of hexane extract of Magnolia sieboldii (MsHE) were conducted on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. The ameliorative effects of MsHE on esophageal damage in rats induced by gastric acid reflux was explored in vivo. The results showed that MsHE decreased the production of nitric oxide (NO) and expression levels of iNOS, COX-2 and TNF-α on LPS-stimulated RAW 264.7 cells and MsHE treatment ameliorated the rats' esophageal tissue damage induced by gastric acid and inhibited the increase of inflammatory mediators and pro-inflammatory cytokines by regulating NF-κB signaling pathway. In addition, MsHE protected the function of barrier of epithelial cells against inflammatory conditions through increasing the expression of tight junctions. Furthermore, liquid chromatography-mass spectrometry analysis was used for determine the active ingredients contained in MsHE. The results show that MsHE can alleviate experimental rat RE by regulating NF-κB signaling pathway. In summary, MsHE may be used as a source material of drug candidate for the treatment of RE.

Silibinin Attenuates Silica Dioxide Nanoparticles-Induced Inflammation by Suppressing TXNIP/MAPKs/AP-1 Signaling.

Silica dioxide nanoparticles (SiONPs) have been applied to several fields, such as drug delivery and gene therapy. However, SiONPs are a constituent of fine dust and can induce excessive inflammatory responses in the lungs via the airways. Silibinin, a major component of silymarin, has been known for its anti-oxidant and anti-inflammatory effects. In the present study, we explored the protective effects of silibinin against SiONPs-induced airway inflammation and explored its underlying mechanism of action, focusing on thioredoxin-interacting protein (TXNIP)/mitogen-activated protein kinases (MAPKs) in vitro and in vivo. In SiONPs-stimulated NCI-H292 airway epithelial cells, silibinin treatment effectively suppressed the elevation of the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß, which was accompanied by the reduction in the expression of TXNIP, MAPKs, and activator protein-1 (AP-1). In SiONPs-treated mice, silibinin administration inhibited the increase in inflammatory cell counts and proinflammatory mediators, and it alleviated airway inflammation by SiONPs exposure. In addition, silibinin administration effectively suppressed the elevation of TXNIP/MAPKs/AP-1 signaling by SiONPs exposure. Taken together, silibinin effectively inhibited SiONPs-induced inflammatory responses, and this effect was closely related to the inhibition of TXNIP/MAPK/AP-1 signaling. These results suggested that silibinin might be useful for reducing pulmonary inflammation induced by SiONPs.

Correction: Akanda, M.R., et al., Anti-Inflammatory and Gastroprotective Roles of Rabdosia inflexa through Downregulation of Pro-Inflammatory Cytokines and MAPK/NF-κB Signaling Pathways. Int. J. Mol. Sci. 2018, 19, 584.

The authors wish to make the following corrections to this paper [...].