Potential of Gut Microbial Metabolites in Treating Osteoporosis and Obesity: A Network Pharmacology and Bioinformatics Approach.

BACKGROUND The gut microbial metabolites demonstrate significant activity against metabolic diseases including osteoporosis (OP) and obesity, but active compounds, targets, and mechanisms have not been fully identified. Hence, the current investigation explored the mechanisms of active metabolites and targets against OP and obesity by using network pharmacology approaches. MATERIAL AND METHODS The gutMGene database was used to collect gut microbial targets-associated metabolites; DisGeNET and OMIM databases were used to identify targets relevant to OP and obesity. A total of 63 and 89 overlapped targets were considered the final OP and obesity targets after creating a Venn diagram of metabolites-related targets and disease-related targets. Furthermore, the top 20% of degrees, betweenness, and closeness were used to form the sub-network of protein-protein interaction of these targets. Finally, the biotransformation-increased receptors and biological mechanisms were identified and validated using ADMET properties analysis, molecular docking, and molecular dynamic simulation. RESULTS GO, KEGG pathway analysis, and protein-protein interactions were performed to establish metabolites and target networks. According to the enrichment analysis, OP and obesity are highly linked to the lipid and atherosclerosis pathways. Moreover, ADMET analysis depicts that the major metabolites have drug-likeliness activity and no or less toxicity. Following that, the molecular docking studies showed that compound K and TP53 target have a remarkable negative affinity (-8.0 kcal/mol) among all metabolites and targets for both diseases. Finally, the conformity of compound K against the targeted protein TP53 was validated by 250ns MD simulation. CONCLUSIONS Therefore, we summarized that compound K can regulate TP53 and could be developed as a therapy option for OP and obesity.

Bioconversion, Pharmacokinetics, and Therapeutic Mechanisms of Ginsenoside Compound K and Its Analogues for Treating Metabolic Diseases.

Rare ginsenoside compound K (CK) is an intestinal microbial metabolite with a low natural abundance that is primarily produced by physicochemical processing, side chain modification, or metabolic transformation in the gut. Moreover, CK exhibits potent biological activity compared to primary ginsenosides, which has raised concerns in the field of ginseng research and development, as well as ginsenoside-related dietary supplements and natural products. Ginsenosides Rb1, Rb2, and Rc are generally used as a substrate to generate CK via several bioconversion processes. Current research shows that CK has a wide range of pharmacological actions, including boosting osteogenesis, lipid and glucose metabolism, lipid oxidation, insulin resistance, and anti-inflammatory and anti-apoptosis properties. Further research on the bioavailability and toxicology of CK can advance its medicinal application. The purpose of this review is to lay the groundwork for future clinical studies and the development of CK as a therapy for metabolic disorders. Furthermore, the toxicology and pharmacology of CK are investigated as well in this review. The findings indicate that CK primarily modulates signaling pathways associated with AMPK, SIRT1, PPARs, WNTs, and NF-kB. It also demonstrates a positive therapeutic effect of CK on non-alcoholic fatty liver disease (NAFLD), obesity, hyperlipidemia, diabetes, and its complications, as well as osteoporosis. Additionally, the analogues of CK showed more bioavailability, less toxicity, and more efficacy against disease states. Enhancing bioavailability and regulating hazardous variables are crucial for its use in clinical trials.

The Effects of Body Fat Reduction through the Metabolic Control of Steam-Processed Ginger Extract in High-Fat-Diet-Fed Mice.

The prevalence of metabolic syndrome is increasing globally due to behavioral and environmental changes. There are many therapeutic agents available for the treatment of chronic metabolic diseases, such as obesity and diabetes, but the data on their efficacy and safety are lacking. Through a pilot study by our group, Zingiber officinale rhizomes used as a spice and functional food were selected as an anti-obesity candidate. In this study, steam-processed ginger extract (GGE) was used and we compared its efficacy at alleviating metabolic syndrome-related symptoms with that of conventional ginger extract (GE). Compared with GE, GGE (25-100 µg/mL) had an increased antioxidant capacity and α-glucosidase inhibitory activity in vitro. GGE was better at suppressing the differentiation of 3T3-L1 adipocytes and lipid accumulation in HepG2 cells and promoting glucose utilization in C2C12 cells than GE. In 16-week high-fat-diet (HFD)-fed mice, GGE (100 and 200 mg/kg) improved biochemical profiles, including lipid status and liver function, to a greater extent than GE (200 mg/kg). The supplementation of HFD-fed mice with GGE (200 mg/kg) resulted in the downregulation of SREBP-1c and FAS gene expression in the liver. Collectively, our results indicate that GGE is a promising therapeutic for the treatment of obesity and metabolic syndrome.

A review on Impact of dietary interventions, drugs, and traditional herbal supplements on the gut microbiome.

The gut microbiome is the community of healthy, and infectious organisms in the gut and its interaction in the host gut intestine (GI) environment. The balance of microbial richness with beneficial microbes is very important to perform healthy body functions like digesting food, controlling metabolism, and precise immune function. Alternately, this microbial dysbiosis occurs due to changes in the physiochemical condition, substrate avidity, and drugs. Moreover, various categories of diet such as "plant-based", "animal-based", "western", "mediterranean", and various drugs (antibiotic and common drugs) also contribute to maintaining microbial flora inside the gut. The imbalance (dysbiosis) in the microbiota of the GI tract can cause several disorders (such as diabetes, obesity, cancer, inflammation, and so on). Recently, the major interest is to use prebiotic, probiotic, postbiotic, and herbal supplements to balance such microbial community in the GI tract. But, there has still a large gap in understanding the microbiome function, and its relation to the host diet, drugs, and herbal supplements to maintain the healthy life of the host. So, the present review is about the updates on the microbiome concerns related to diet, drug, and herbal supplements, and also gives research evidence to improve our daily habits regarding diet, drugs, and herbal supplements. Because our regular dietary plan and traditional herbal supplements can improve our health by balancing the bacteria in our gut.

Hydroponic Ginseng ROOT Mediated with CMC Polymer-Coated Zinc Oxide Nanoparticles for Cellular Apoptosis via Downregulation of BCL-2 Gene Expression in A549 Lung Cancer Cell Line.

The unique and tailorable physicochemical features of zinc oxide nanoparticles (ZnO-NPs) synthesized from green sources make them attractive for use in cancer treatment. Hydroponic-cultured ginseng-root-synthesized ZnO-NPs (HGRCm-ZnO NPs) were coated with O-carboxymethyl chitosan (CMC) polymer, which stabilized and enhanced the biological efficacy of the nanoparticles. Nanoparticles were characterized by X-ray diffraction (XRD), UV-Vis spectroscopy, transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and energy-dispersive X-ray spectroscopy (EDS). The flower-shaped nanoparticles were crystalline in nature with a particle size of 28 nm. To evaluate if these NPs had anti-lung cancer activity, analysis was performed on a human lung carcinoma cell line (A549). HGRCm-ZnO nanoparticles showed less toxicity to normal keratinocytes (HaCaTs), at concentrations up to 20 µg/mL, than A549 cancer cells. Additionally, these NPs showed dose-dependent colony formation and cell migration inhibition ability, which makes them more promising for lung cancer treatment. Additionally, Hoechst and propidium iodide dye staining also confirmed that the NP formulation had apoptotic activity in cancer cells. Further, to evaluate the mechanism of cancer cell death via checking the gene expression, HGRCm ZnO NPs upregulated the BAX and Caspase 3 and 9 expression levels but downregulated Bcl-2 expression, indicating that the nanoformulation induced mitochondrial-mediated apoptosis. Moreover, these preliminary results suggest that HGRCm ZnO NPs can be a potential candidate for future lung cancer treatment.

A Focused Review on Molecular Signalling Mechanisms of Ginsenosides Anti-Lung Cancer and Anti-inflammatory Activities.

BACKGROUND: Ginseng (Panax ginseng Meyer) is a cultivated medicinal herb that has been widely available in the Asian region since the last century. Ginseng root is used worldwide in Oriental medicine. Currently, the global mortality and infection rates for lung cancer and inflammation are significantly increasing. Therefore, various preventative methods related to the activity of ginsenosides have been used for lung cancer as well as inflammation. METHODS: Web-based searches were performed on Web of Science, Springer, PubMed, and Scopus. A cancer statistical analysis was also conducted to show the current ratio of affected cases and death from lung cancer around the world. RESULTS: Ginsenosides regulate the enzymes that participate in tumor growth and migration, such as nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK), extracellular signalregulated kinases 1/2 (ERK1/2), the gelatinase network metalloproteinase-2 (MMP-2/9) and activator protein 1 (AP-1). In addition, ginsenosides also possess anti-inflammatory effects by inhibiting the formation of proinflammatory cytokines (tumor necrosis factor-α) (TNF-α) and interleukin-1ß (IL-1ß) and controlling the activities of inflammatory signalling pathways, such as NF-κB, Janus kinase2/signal transducer, and activator of transcription 3 (Jak2/Stat3). CONCLUSION: In several in vitro and in vivo models, P. ginseng showed potential beneficial effects in lung cancer and inflammation treatment. In this review, we provide a detailed and up-to-date summary of research evidence for antilung cancer and anti-inflammatory protective effects of ginsenosides and their potential molecular mechanisms.

Investigating the Anticancer Activity of G-Rh1 Using In Silico and In Vitro Studies (A549 Lung Cancer Cells).

Ginsenoside Rh1 (G-Rh1), a possible bioactive substance isolated from the Korean Panax ginseng Meyer, has a wide range of pharmacological effects. In this study, we have investigated the anticancer efficacy of G-Rh1 via in silico and in vitro methodologies. This study mainly focuses on the two metastatic regulators, Rho-associated protein kinase 1 (ROCK1) and RhoA, along with other standard apoptosis regulators. The ROCK1 protein is a member of the active serine/threonine kinase family that is crucial for many biological processes, including cell division, differentiation, and death, as well as many cellular processes and muscle contraction. The abnormal activation of ROCK1 kinase causes several disorders, whereas numerous studies have also shown that RhoA is expressed highly in various cancers, including colon, lung, ovarian, gastric, and liver malignancies. Hence, inhibiting both ROCK1 and RhoA will be promising in preventing metastasis. Therefore, the molecular level interaction of G-Rh1 with the ROCK1 and RhoA active site residues from the preliminary screening clearly shows its inhibitory potential. Molecular dynamics simulation and principal component analysis give essential insights for comprehending the conformational changes that result from G-Rh1 binding to ROCK1 and RhoA. Further, MTT assay was employed to examine the potential cytotoxicity in vitro against human lung cancer cells (A549) and Raw 264.7 Murine macrophage cells. Thus, G-Rh1 showed significant cytotoxicity against human lung adenocarcinoma (A549) at 100 µg/mL. In addition, we observed an elevated level of reactive oxygen species (ROS) generation, perhaps promoting cancer cell toxicity. Additionally, G-Rh1 suppressed the mRNA expression of RhoA, ROCK1, MMP1, and MMP9 in cancer cell. Accordingly, G-Rh1 upregulated the p53, Bax, Caspase 3, caspase 9 while Bcl2 is downregulated intrinsic pathway. The findings from our study propose that the anticancer activity of G-Rh1 may be related to the induction of apoptosis by the RhoA/ROCK1 signaling pathway. As a result, this study evaluated the functional drug-like compound G-Rh1 from Panax ginseng in preventing and treating lung cancer adenocarcinoma via regulating metastasis and apoptosis.

Production of Minor Ginsenoside CK from Major Ginsenosides by Biotransformation and Its Advances in Targeted Delivery to Tumor Tissues Using Nanoformulations.

For over 2000 years, ginseng (roots of Panax ginseng C.A. Meyer) has been used as a traditional herbal medicine. Ginsenosides are bioactive compounds present in ginseng responsible for the pharmacological effects and curing various acute diseases as well as chronic diseases including cardiovascular disease, cancer and diabetes. Structurally, ginsenosides consist of a hydrophobic aglycone moiety fused with one to four hydrophilic glycoside moieties. Based on the position of sugar units and their abundance, ginsenosides are classified into major and minor ginsenosides. Despite the great potential of ginsenosides, major ginsenosides are poorly absorbed in the blood circulation, resulting in poor bioavailability. Interestingly, owing to their small molecular weight, minor ginsenosides exhibit good permeability across cell membranes and bioavailability. However, extremely small quantities of minor ginsenosides extracted from ginseng plants cannot fulfill the requirement of scientific and clinical studies. Therefore, the production of minor ginsenosides in mass production is a topic of interest. In addition, their poor solubility and lack of targetability to tumor tissues limits their application in cancer therapy. In this review, various methods used for the transformation of major ginsenosides to minor ginsenoside compound K (CK) are summarized. For the production of CK, various transformation methods apply to major ginsenosides. The challenges present in these transformations and future research directions for producing bulk quantities of minor ginsenosides are discussed. Furthermore, attention is also paid to the utilization of nanoformulation technology to improve the bioavailability of minor ginsenoside CK.

Anti-influenza A virus activity by Agrimonia pilosa and Galla rhois extract mixture.

Influenza A virus (IAV) continues to threaten human health. To date, two classes of antiviral drugs have been approved to treat IAV infection, but the continuous emergence of the drug-resistant IAV mutant reinforces the need to develop new antiviral drugs. In this study, we aimed to investigate the anti-IAV activity of an aqueous mixture of Agrimonia pilosa and Galla rhois extracts (APRG64). We demonstrated that APRG64 significantly reduced the IAV-induced cytopathic effect, the transcription/expression of viral proteins, and the production of infectious viral particles. Among nine major components of APRG64, apigenin was identified as the main ingredient responsible for the anti-IAV activity. Interestingly, APRG64 and apigenin inhibited the cell attachment and entry of virus and polymerase activity. Importantly, intranasal administration of APRG64 or apigenin strongly reduced viral loads in the lungs of IAV-infected mice. Furthermore, oral administration of APRG64 significantly reduced the level of viral RNAs and the expression level of pro-inflammatory cytokines in the lungs, which protected mice from IAV-induced mortality. In conclusion, APRG64 could be an attractive antiviral drug to treat IAV infection.

Binary Effects of Gynostemma Gold Nanoparticles on Obesity and Inflammation via Downregulation of PPARγ/CEPBα and TNF-α Gene Expression.

Nanoscience is a multidisciplinary skill with elucidated nanoscale particles and their advantages in applications to various fields. Owing to their economical synthesis, biocompatible nature, and widespread biomedical and environmental applications, the green synthesis of metal nanoparticles using medicinal plants has become a potential research area in biomedical research and functional food formulations. Gynostemma pentaphyllum (GP) has been extensively used in traditional Chinese medicine to cure several diseases, including diabetes mellitus (DM). This is the first study in which we examined the efficacy of G. pentaphyllum gold nanoparticles (GP-AuNPs) against obesity and related inflammation. GP extract was used as a capping agent to reduce Au2+ to Au0 to form stable gold nanoparticles. The nanoparticles were characterized by using UV-VIS spectroscopy, and TEM images were used to analyze morphology. In contrast, the existence of the functional group was measured using FTIR, and size and shape were examined using XRD analysis. In vitro analysis on GP-AuNPs was nontoxic to RAW 264.7 cells and 3T3-L1 cells up to a specific concentration. It significantly decreased lipid accumulation in 3T3-L1 obese and reduced NO production in Raw 264.7 macrophage cells. The significant adipogenic genes PPARγ and CEPBα and a major pro-inflammatory cytokine TNF-α expression were quantified using RT-PCR. The GP-AuNPs decreased the face of these genes remarkably, revealing the antiadipogenic and anti-inflammatory activity of our synthesized GP-AuNPs. This study represents thorough research on the antiobesity effect of Gynostemma pentaphyllum gold nanoparticles synthesized using a green approach and the efficacy instead of related inflammatory responses.

Metabolite profiling of a Sargassum micracanthum methanol extract with in vitro efficacy against human head and neck squamous cell carcinoma aggressiveness.

OBJECTIVE: Extracts from the brown algae Sargassum micracanthum have documented anti-viral, anti-oxidant, and anti-inflammatory activities as well as potential anti-tumor efficacy against several cancer types. Here, we evaluated the inhibitory effect and molecular mechanisms of methanol extract of S. micracanthum (MESM) on the aggressiveness of human head and neck squamous cell carcinoma (HNSCC) using in vitro cell culture-based models. DESIGN: To test the potential efficacy of MESM on the migratory and invasive properties of HNSCC cells, we used wound healing, transwell cell migration and invasion assays. Proteome profiling and functional in silico analysis were applied to investigate the possible modes of action by MESM. We also examined the metabolite profiling of MESM using gas chromatography/mass spectrometry. RESULTS: MESM inhibited the motility of human HNSCC cell lines as well as invasiveness without influencing cell survival. Proteome profiling identified 19 oncogenic proteins significantly downregulated by MESM treatment. Protein-protein interaction network and gene ontology analyses revealed that Tie2 and associated angiogenic signaling pathway components were significantly enriched among these downregulated oncogenic proteins, which was confirmed by validating the reduced Tie2 expression in MESM treatment groups. Metabolite profiling of MESM identified six-carbon sugar alcohols such as D-sorbitol and/or D-mannitol as the main bioactive compounds. D-sorbitol and D-mannitol effectively reduced Tie2 expression and the aggressiveness of human HNSCC cell lines. CONCLUSIONS: These findings suggest that six-carbon sugar alcohols in MESM have promising anti-cancer efficacy for the treatment of human HNSCC and further identify Tie2 signaling components as potential treatment targets.

Potent antiviral activity of the extract of Elaeocarpus sylvestris against influenza A virus in vitro and in vivo.

BACKGROUND: Elaeocarpus sylvestris (Lour.) Poir. (Elaeocarpaceae) belongs to a genus of tropical and semitropical evergreen trees, which has known biological activities such as antiviral and immunomodulatory activities. However, its antiviral potential against influenza virus infection remains unknown. PURPOSE: In this study, we investigated the antiviral activity of the 50% aqueous ethanolic extract of E. sylvestris (ESE) against influenza A virus (IAV) infection, which could lead to the development of novel phytomedicine to treat influenza virus infection. METHODS: To investigate the in vitro antiviral activity of ESE and its main ingredients, 1,​2,​3,​4,​6-​penta-​O-​galloyl-ß-d-glucose (PGG) and geraniin (GE), the levels of viral RNAs, proteins, and infectious viral particles in IAV-infected MDCK cells were analyzed. Molecular docking analysis was performed to determine the binding energy of PGG and GE for IAV proteins. To investigate in vivo antiviral activity, IAV-infected mice were treated intranasally or intragastrically with ESE, PGG, or GE. RESULTS: ESE and its gallate main ingredients (PGG and GE) strongly inhibited the production of viral RNAs, viral proteins, and infectious viral particles in vitro. Also through the viral attachment on cells, polymerase activity, signaling pathway, we revealed the ESE, PGG, and GE inhibit multiple steps of IAV replication. Molecular docking analysis revealed that PGG and GE could interact with 12 key viral proteins (M1, NP, NS1 effector domain (ED), NS1 RNA-binding domain (RBD), HA pocket A, HA receptor-binding domain (RBD), NA, PA, PB1, PB2 C-terminal domain, PB2 middle domain, and PB2 cap-binding domain) of IAV proteins with stable binding energy. Furthermore, intranasal administration of ESE, PGG, or GE protected mice from IAV-induced mortality and morbidity. Importantly, oral administration of ESE suppressed IAV replication and the expression of inflammatory cytokines such as IFN-γ, TNF-α, and IL-6 in the lungs to a large extent. CONCLUSION: ESE and its major components (PGG and PE) exhibited strong antiviral activity in multiple steps against IAV infection in silico, in vivo, and in vitro. Therefore, ESE could be used as a novel natural product derived therapeutic agent to treat influenza virus infection.

Preclinical evaluation of Zanthoxylum piperitum Benn., traditional muscle pain remedy, for joint inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum piperitum has been used as a traditional Asian medicine to treat hypertension, stroke, bruise and muscle pain. It has been known to induce detoxification; affect anti-bacterial, anti-oxidant, and tyrosinase activity; inhibit osteosarcoma proliferation; anti-osteoarthritis inflammation. In this study, we aim to identify the therapeutic effect of Z. piperitum 90% EtOH extract (ZPE-LR) on rheumatoid arthritis. MATERIAL AND METHODS: We investigated the anti-rheumatoid arthritis and -immunomodulatory activities of the ZPE-LR in collagen-induced arthritic (CIA) mice, a rheumatoid arthritis animal model. In order to assess the analgesic effects of ZPE-LR in vivo, acetic acid injection, formaldehyde injection, hot plate model was used. The mechanism for anti-inflammatory activity of ZPE-LR was identified with LPS-stimulated Raw 264.7 cells. RESULTS: Pharmacologically, oral administration of ZPE-LR into CIA mice resulted in a significant and dose-dependent decrease in clinical arthritis score and paw swelling compared to untreated negative control. Pathologic examination showed that ZPE-LR prevented morphological change in cartilage and destruction of phalanges in CIA mice. This protective effect was associated with reduced pain, inflammatory mediators such as NO, TNF-α, IL-1ß, and IL-6, as well as COX-2 and iNOS expression. Furthermore, reduction of phosphor-ERK and BDNF indicates a novel rheumatoid arthritis-regulating mechanism by ZPE-LR treatment. CONCLUSIONS: These data suggest that the administration of ZPE-LR remarkably inhibited CIA progression and might be helpful in suppressing inflammation and pain in rheumatoid arthritis.

Anti-varicella zoster virus and related anti-inflammation effects of ethanolic extract of Elaeocarpus sylvestris.

ETHNOPHARMACOLOGICAL RELEVANCE: Elaeocarpus sylvestris var. ellipticus (ES), a plant that grows in Taiwan, Japan, and Jeju Island in Korea. ES root bark, known as "sanduyoung," has long been used in traditional oriental medicine. ES is also traditionally used to treat anxiety, asthma, arthritis, stress, depression, palpitation, nerve pain, epilepsy, migraine, hypertension, liver diseases, diabetes, and malaria. However, lack of efficacy and mechanism studies on ES. AIM OF THE STUDY: In the present study, we aim to investigate the VZV-antiviral efficacy, pain suppression, and the anti-inflammatory and antipyretic effects of ES. METHODS: and methods: Inhibition of VZV was evaluated by hollow fiber assays. Analgesic and antipyretic experiments were conducted using ICR mice and SD Rats, and anti-inflammatory experiments were conducted using Raw264.7 cells. RESULTS: To evaluate the efficacy of ESE against VZV, we conducted antiviral tests. ESE inhibited cell death by disrupting virus and gene expression related to invasion and replication. In addition, ESE suppressed the pain response as measured by writhing and formalin tests and suppressed LPS-induced inflammatory fever. Further, ESE inhibited the phosphorylation of IκB and NF-κB in LPS-induced Raw264.7 cells and expression of COX-2, iNOS, IL-1ß, IL-6, and TNF-α. CONCLUSION: E. sylvestris shows potential as a source of medicine. ESE had a direct effect on VZV and an inhibitory effect on the pain and inflammation caused by VZV infection.

Lomens-P0 (mixed extracts of Hordeum vulgare and Chrysanthemum zawadskii) regulate the expression of factors affecting premenstrual syndrome symptoms.

BACKGROUND/OBJECTIVES: Premenstrual syndrome (PMS) is a disorder characterized by repeated emotional, behavioral, and physical symptoms before menstruation, and the exact cause and mechanism are uncertain. Hyperprolactinemia interferes with the normal production of estrogen and progesterone, leading to PMS symptoms. Thus, we judged that the inhibition of prolactin hypersecretion could mitigate PMS symptoms. MATERIALS/METHODS: Hordeum vulgare L. extract (HVE), Chrysanthemum zawadskii var. latilobum extract (CZE), and Lomens-P0 the mixture of these extracts were tested in subsequent experiments. The effect of extracts on prolactin secretion at the in vitro level was measured in GH3 cells. Nitric oxide and pro-inflammatory mediator expression were measured in RAW 264.7 cells to confirm the anti-inflammatory effect. Also, the hyperprolactinemic Institute for Cancer Research (ICR) mice model was used to measure extract effects on prolactin and hormone secretion and uterine inflammation. RESULTS: Anti-inflammatory effects of and prolactin secretion suppress by HVE and CZE were confirmed through in vitro experiments (P < 0.05). Treatment with Lomens-P0 inhibited prolactin secretion (P < 0.05) and restored normal sex hormone secretion in the hyperprolactinemia mice model. In addition, extracts significantly inhibited the expression of pro-inflammatory biomarkers, including interleukin-1ß, and -6, tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2 (P < 0.01). We used high-performance liquid chromatography analyses to identify tricin and chlorogenic acid as the respective components of HVE and CZE that inhibit prolactin secretion. The Lomens-P0, which includes tricin and chlorogenic acid, is expected to be effective in improving PMS symptoms in the human body. CONCLUSIONS: The Lomens-P0 suppressed the prolactin secretion in hyperprolactinemia mice, normalized the sex hormone imbalance, and significantly suppressed the expression of inflammatory markers in uterine tissue. This study suggests that Lomens-P0 may have the potential to prevent or remedy materials to PMS symptoms.

A Comparative Study of the Hepatoprotective Effect of Centella asiatica Extract (CA-HE50) on Lipopolysaccharide/d-galactosamine-Induced Acute Liver Injury in C57BL/6 Mice.

Acute liver failure (ALF) refers to the sudden loss of liver function and is accompanied by several complications. In a previous study, we revealed the protective effect of Centella asiatica 50% ethanol extract (CA-HE50) on acetaminophen-induced liver injury. In the present study, we investigate the hepatoprotective effect of CA-HE50 in a lipopolysaccharide/galactosamine (LPS-D-Gal)-induced ALF animal model and compare it to existing therapeutic silymarin, Lentinus edodes mycelia (LEM) extracts, ursodeoxycholic acid (UDCA) and dimethyl diphenyl bicarboxylate (DDB). Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were decreased in the CA-HE50, silymarin, LEM, UDCA and DDB groups compared to the vehicle control group. In particular, AST and ALT levels of the 200 mg/kg CA-HE50 group were significantly decreased compared to positive control groups. Lactate dehydrogenase (LDH) levels were significantly decreased in the CA-HE50, silymarin, LEM, UDCA and DDB groups compared to the vehicle control group and LDH levels of the 200 mg/kg CA-HE50 group were similar to those of the positive control groups. Superoxide dismutase (SOD) activity was significantly increased in the 100 mg/kg CA-HE50, LEM and UDCA groups compared to the vehicle control group and, in particular, the 100 mg/kg CA-HE50 group increased significantly compared to positive control groups. In addition, the histopathological lesion score was significantly decreased in the CA-HE50 and positive control groups compared with the vehicle control group and the histopathological lesion score of the 200 mg/kg CA-HE50 group was similar to that of the positive control groups. These results show that CA-HE50 has antioxidant and hepatoprotective effects at a level similar to that of silymarin, LEM, UDCA and DDB, which are known to have hepatoprotective effects; further, CA-HE50 has potential as a prophylactic and therapeutic agent in ALF.

Hydroponic Cultured Ginseng Leaves Zinc Oxides Nanocomposite Stabilized with CMC Polymer for Degradation of Hazardous Dyes in Wastewater Treatment.

This study demonstrated the synthesis of o-carboxymethyl chitosan (CMC)-stabilized zinc oxide nanocomposites (ZnO NCs) combined with aqueous leaves extracts of hydroponically cultured ginseng and used as a photocatalyst for the degradation of hazardous dyes, including malachite green (MG), rhodamine B (RB), and congo red (CR) under ultraviolet illumination. Hydroponic ginseng leaves contain bioactive components, namely ginsenoside and natural polyphenol, which prompt ginseng's biological effect. Besides, the CMC polymer is naturally biodegradable, stabilizes the nanoformation and enhances the solubility of ginsenoside. The hydroponic ginseng leaves zinc oxide CMC nanocomposites (GL-CMC-ZnO NCs) were synthesized using the co-precipitation method and characterized using different analytical methods. The FTIR analysis identified significant phytochemicals in the leaves extracts and cotton-shape morphology observed using FE-TEM analysis. The XRD analysis also determined that the crystallite size was 28 nm. The photocatalyst degraded CR, RB, and MG dyes by approximately 87%, 94%, and 96% within contact times of 10, 20, 25, and 30 min, respectively, when the dye concentration was 15 mg/L. As far as our knowledge, this is the first report on hydroponic ginseng NCs incorporated with the CMC polymer for the degradation of hazardous dyes on wastewater treatment. This study can add significant value to large-scale wastewater treatment.

Safety, tolerability of ES16001, a novel varicella zoster virus reactivation inhibitor, in healthy adults.

PURPOSE: Herpes zoster (HZ), or shingles, is a clinical syndrome resulting from the reactivation of latent varicella zoster virus (VZV) within the sensory ganglia. We evaluated the safety and tolerability of ES16001 (ethanol extract of Elaeocarpus sylvestris var. ellipticus), a novel inhibitor of varicella zoster virus reactivation in healthy adults. METHOD: Single-center, randomized, double-blind, placebo-controlled, single and multiple ascending dose (SAD and MAD, respectively) studies were conducted in 20- to 45-year-old healthy adults without chronic disease. In the SAD study (n = 32), subjects randomly received a single oral dose of 240, 480, 960, or 1440 mg ES16001 or a placebo. In the MAD study (n = 16), subjects randomly received once daily doses of 480 or 960 mg ES16001 or a placebo for 5 days. The safety and tolerability of the drug were evaluated by monitoring participants' treatment emergent adverse events (TEAEs) and vital signs, electrocardiograms (ECGs), physical examinations, and clinical laboratory tests. RESULTS: In the SAD study, 11 adverse reactions were seen in 5 subjects, and in the MAD study, 8 adverse reactions were seen in 6 subjects. All adverse reactions were mild, and no serious adverse reactions occurred. The most common adverse reaction was an increase in alanine aminotransferase (ALT), but all test values were in the clinically non-significant range, and their clinical significance was judged to be small considering the fact that most of the test values returned to normal immediately after the end of drug administration. CONCLUSION: ES16001 has good safety and tolerability when administered both once and repeatedly to healthy subjects. Further research is needed to identify any possible drug-induced hepatotoxicity, which appears infrequently. Our findings provide a rationale for further clinical investigations of ES16001 for the prevention of HZ. TRIAL REGISTRATION: CRIS, KCT0006066. Registered 7 April 2021-Retrospectively registered, https://cris.nih.go.kr/cris/search/detailSearch.do/19071 ).

Potent antiviral activity of Agrimonia pilosa, Galla rhois, and their components against SARS-CoV-2.

Agrimonia pilosa (AP), Galla rhois (RG), and their mixture (APRG64) strongly inhibited SARS-CoV-2 by interfering with multiple steps of the viral life cycle including viral entry and replication. Furthermore, among 12 components identified in APRG64, three displayed strong antiviral activity, ursolic acid (1), quercetin (7), and 1,2,3,4,6-penta-O-galloyl-ß-d-glucose (12). Molecular docking analysis showed these components to bind potently to the spike receptor-binding-domain (RBD) of the SARS-CoV-2 and its variant B.1.1.7. Taken together, these findings indicate APRG64 as a potent drug candidate to treat SARS-CoV-2 and its variants.

Synthesis and characterization of glycol chitosan coated selenium nanoparticles acts synergistically to alleviate oxidative stress and increase ginsenoside content in Panax ginseng.

The objective of the present study is synthesis of glycol chitosan coated selenium nanoparticles (GC-Se NPs) and evaluation of oxidative stress and ginsenoside accumulation in P. ginseng C. A. Meyer. We synthesized (Se NPs and GC-Se NPs) and characterized using various spectroscopic analyses. The highest concentration (20 mg L-1) of GC-Se NPs induced moderate ROS (O2- and H2O2) accumulation and upregulation of PgSOD and PgCAT showing good biocompatibility and less toxicity at the highest concentration. Furthermore, ginsenoside biosynthetic pathway genes (PgHMGR, PgSS, PgSE, PgDDS) also showed significant upregulation upon 20 mg L-1 GC-Se NPs treatment. At 20 mg L-1 GC-Se NPs treatment, ginsenoside accumulated upto 217.47 mg/mL and 169.86 mg/mL mainly due to the increased proportion of Rb1 and Re ginsenosides. Altogether, our results suggested that ecofriendly conjugation of GC with Se NPs could be used as a bio fortifier to enhance the ginsenoside profile and to increase the quality of ginseng roots.