Antiviral Effects of Secondary Metabolites from Jatropha podagrica Leaves against the Pseudotyped Virus of SARS-CoV-2 Omicron.

Jatropha podagrica holds a longstanding place in traditional herbal medicine, primarily utilized for addressing skin infections, acting as antipyretics, diuretics, and purgatives. In this study, our primary objective was to investigate the secondary metabolites present in J. podagrica leaves, with the aim of pinpointing natural compounds exhibiting potential antiviral activities. Five secondary metabolites (1-5), including an auronol glycoside (1), two coumarins (2 and 3), a chromane (4) and a gallotannin (5), were isolated from J. podagrica leaves. Compound 1 presented as an amalgamation of unseparated mixtures, yet its intricate composition was adroitly unraveled through the strategic deployment of a chiral HPLC column. This tactic yielded the isolation of epimers (+)-1 and (-)-1, ascertained as unreported auronol glycosides. The structures of these novel compounds, (+)-1 and (-)-1, were elucidated to be (2S)-hovetrichoside C [(+)-1] and (2R)-hovetrichoside C [(-)-1] through NMR data and HR-ESIMS analyses, enzymatic hydrolysis, and comparison of optical rotation values. Cytotoxicity and antiviral effects were assessed for the isolated compounds ((+)-1, (-)-1 and 2-5), along with compound 1a (the aglycone of 1), in the A549 human alveolar basal epithelial cell line. Each compound demonstrated a cell viability of approximately 80% or higher, confirming their non-toxic nature. In the group of compounds, compounds 3-5 demonstrated antiviral effects based on RT-qPCR results, with individual enhancements ranging from approximately 28 to 38%. Remarkably, compound 4 exhibited the most substantial antiviral effect. Utilization of compound 4 to assess immune boosting and anti-inflammatory effects revealed increased levels of STING, RIG-I, NLRP3, and IL-10 along with a decrease in TNF-α and IL-6. Therefore, these findings underscore the potential of these active compounds 3-5 not only as therapeutic agents for SARS-CoV-2 but also as new contenders for upcoming pandemics.

Inonotus obliquus upregulates muscle regeneration and augments function through muscle oxidative metabolism.

Skeletal muscle wasting related to aging or pathological conditions is critically associated with the increased incidence and prevalence of secondary diseases including cardiovascular diseases, metabolic syndromes, and chronic inflammations. Much effort is made to develop agents to enhance muscle metabolism and function. Inonotus obliquus (I. obliquus; IO) is a mushroom popularly called chaga and has been widely employed as a folk medicine for inflammation, cardiovascular diseases, diabetes, and cancer in Eastern Europe and Asia. However, its effect on muscle health has not been explored. Here, we aimed to investigate the beneficial effect of IO extract in muscle regeneration and metabolism. The treatment of IO in C2C12 myoblasts led to increased myogenic differentiation and alleviation of dexamethasone-induced myotube atrophy. Network pharmacological analysis using the identified specific chemical constituents of IO extracts predicted protein kinase B (AKT)-dependent mechanisms to promote myogenesis and muscle regeneration. Consistently, IO treatment resulted in the activation of AKT, which suppressed muscle-specific ubiquitin E3 ligases induced by dexamethasone. IO treatment in mice improved the regeneration of cardiotoxin-injured muscles accompanied by elevated proliferation and differentiation of muscle stem cells. Furthermore, it elevated the mitochondrial content and muscle oxidative metabolism accompanied by the induction of peroxisome proliferator-activated receptor γ coactivator α (PGC-1α). Our current data suggest that IO is a promising natural agent in enhancing muscle regenerative capacity and oxidative metabolism thereby preventing muscle wasting.

Phytochemical Investigation of Equisetum arvense and Evaluation of Their Anti-Inflammatory Potential in TNFα/INFγ-Stimulated Keratinocytes.

Equisetum arvense L. (Equisetaceae), widely known as 'horsetail', is a perennial plant found extensively across Asia. Extracts of E. arvense have been used in traditional medicine, particularly for the treatment of inflammatory disorders. This study aimed to determine the phytochemical compounds in E. arvense ethanolic extract and their anti-inflammatory properties. Subsequently, we isolated and identified nine secondary metabolites, including kaempferol 3,7-di-O-ß-D-glucopyranoside (1), icariside B2 (2), (Z)-3-hexenyl ß-D-glucopyranoside (3), luteolin 5-O-ß-D-glucopyranoside (4), 4-O-ß-D-glucopyranosyl caffeic acid (5), clemastanin B (6), 4-O-caffeoylshikimic acid (7), (7S,8S)-threo-7,9,9'-trihydroxy-3,3'-dimethoxy-8-O-4'-neolignan-4-O-ß-D-glucopyranoside (8), and 3-O-caffeoylshikimic acid (9). The chemical structures of the isolated compounds (1-9) were elucidated using HR-ESI-MS data, NMR spectra, and ECD data. Next, the anti-inflammatory effects of the isolates were evaluated in tumor necrosis factor (TNF)α/interferon (IFN)γ-induced HaCaT, a human keratinocyte cell line. Among the isolates, compound 3 showed the highest inhibitory effect on the expression of pro-inflammatory chemokines, followed by compounds 6 and 8. Correspondingly, the preceding isolates inhibited TNFα/IFNγ-induced activation of pro-inflammatory transcription factors, signal transducer and activator of transcription 1, and nuclear factor-κB. Collectively, E. arvense could be employed for the development of prophylactic or therapeutic agents for improving dermatitis.

Labdane-type Diterpenes from Pinus eldarica Needles and Their Anti-Helicobacter pylori Activity.

Pinus eldarica is a medicinal tree used in traditional herbal medicine for the treatment of bronchial asthma and various skin diseases. As part of our ongoing search for bioactive phytochemicals with novel structures in natural products, we performed a phytochemical analysis of the methanol (MeOH) extract from P. eldarica needles collected in Iran. Phytochemical investigation of the MeOH extract, aided by liquid chromatography-mass spectrometry-based analysis, resulted in the isolation and identification of three labdane-type diterpenes (1-3), including a new and relatively unique norlabdane-type diterpene with a peroxide moiety, eldaricoxide A (1). The chemical structures of the isolated labdane-type diterpenes were elucidated by analyzing the spectroscopic data from 1D and 2D NMR and high-resolution electrospray ionization-mass spectrometry. The absolute configuration of eldaricoxide A (1) was established by employing a computational method, including electronic circular dichroism calculation and specific optical rotation. An anti-Helicobacter pylori test was conducted, where compound 3 exhibited the most potent antibacterial activity against H. pylori strain 51, inducing 72.7% inhibition (MIC50 value of 92 µM), whereas eldaricoxide A (1) exhibited moderate antibacterial activity against H. pylori strain 51, inducing 54.5% inhibition (MIC50 value of 95 µM). These findings demonstrated that the identified bioactive labdane-type diterpenes 1 and 3 can be applied in the development of novel antibiotics against H. pylori for the treatment of gastric and duodenal ulcers.

Chemical Investigation of Tetradium ruticarpum Fruits and Their Antibacterial Activity against Helicobacter pylori.

The fruit of Tetradium ruticarpum, known as Evodiae Fructus, is a traditional herbal medicine used to treat gastric and duodenal ulcers, vomiting, and diarrhea. The traditional usage can be potentially associated with the antibacterial activity of T. ruticarpum fruits against Helicobacter pylori. However, so far, the antibacterial activity of T. ruticarpum fruits and antibacterial components against H. pylori has not been investigated despite the traditional folk use. The current study was conducted to investigate the bioactive chemical components of T. ruticarpum fruits and evaluate their antibacterial activity against H. pylori. Phytochemical investigation of the EtOH extract of T. ruticarpum fruits led to the isolation and identification of nine compounds (1-9), including phellolactone (1), the absolute configuration of which has not yet been determined. The chemical structures of the isolated compounds were elucidated by analyzing the spectroscopic data from one-dimensional (1D) and two-dimensional (2D) NMR and high-resolution electrospray ionization mass spectrometry (HR-ESIMS) experiments. Specifically, the absolute configuration of compound 1 was established by the application of computational methods, including electronic circular dichroism (ECD) calculation and the NOE/ROE-based interproton distance measurement technique via peak amplitude normalization for the improved cross-relaxation (PANIC) method. In the anti-H. pylori activity test, compound 3 showed the most potent antibacterial activity against H. pylori strain 51, with 94.4% inhibition (MIC50 and MIC90 values of 22 and 50 µM, respectively), comparable to that of metronidazole (97.0% inhibition, and MIC50 and MIC90 values of 17 and 46 µM, respectively). Moreover, compound 5 exhibited moderate antibacterial activity against H. pylori strain 51, with 58.6% inhibition (MIC50 value of 99 µM), which was higher than that of quercetin (34.4% inhibition) as a positive control. Based on the bioactivity results, we also analyzed the structure-activity relationship of the anti-H. pylori activity. Conclusion: These findings demonstrated that T. ruticarpum fruits had antibacterial activity against H. pylori and could be used in the treatment of gastric and duodenal ulcers. Meanwhile, the active compound, 1-methyl-2-(8E)-8-tridecenyl-4(1H)-quinolinone (3), identified herein also indicated the potential application in the development of novel antibiotics against H. pylori.

Daemonorops draco Blume Induces Apoptosis Against Acute Myeloid Leukemia Cells via Regulation of the miR-216b/c-Jun.

Daemonorops draco Blume (DD), also called dragon's blood, has been used as a traditional Korean medicine, especially for relieving pain caused by wound infection. Recently, it has been described that DD has antibacterial and analgesic effects. In this study, the underlying anticancer effect of DD associated with apoptosis was investigated in acute myeloid leukemia cell lines U937 and THP-1. DD exhibited cytotoxic effects and induced apoptosis in U937 and THP-1 cells. Moreover, DD treatment significantly reduced mitochondrial membrane potential (ΔΨ). The protein expression of cleaved poly(ADP-ribose) polymerase, cleaved caspase-3, p-H2A.X, CCAAT/enhancer-binding protein (CHOP), and activating transcription factor 4 was upregulated by DD treatment. Consistently, DD-treated cells had increased reactive oxygen species (ROS) level in a concentration-dependent manner via miR-216b activation in association with c-Jun inhibition. N-acetyl-L-cysteine pretreatment reversed the cytotoxic effect of DD treatment as well as prevented ROS accumulation. Collectively, the results of this study suggest that the anticancer effect of DD in AML was mediated by CHOP-dependent apoptosis along with ROS accumulation and included upregulation of miR-216b followed by a decrease in c-Jun.

Ginkgonitroside, a new nitrophenyl glycoside and bioactive compounds from Ginkgo biloba leaves controlling adipocyte and osteoblast differentiation.

Eight compounds (1-8) including one novel nitrophenyl glycoside, ginkgonitroside (1) were isolated from the leaves of Ginkgo biloba, a popular medicinal plant. The structure of the new compound was characterized using extensive spectroscopic analyses via 1D and 2D NMR data interpretations, HR-ESIMS, and chemical transformation. To the best of our knowledge, the present study is the first to report the presence of nitrophenyl glycosides, which are relatively unique phytochemicals in natural products, in G. biloba. The isolated compounds (1-8) were examined for their effects on the regulation of mesenchymal stem cell (MSC) differentiation. Compounds 1-3 and 8 were able to suppress MSC differentiation toward adipocytes. In contrast, compounds 5 and 8 showed activity promoting osteogenic differentiation of MSCs. These findings demonstrate that the active compounds showed regulatory activity on MSC differentiation between adipocytes and osteocytes.

Ginkwanghols A and B, osteogenic coumaric acid-aliphatic alcohol hybrids from the leaves of Ginkgo biloba.

Ginkgo biloba (Ginkgoaceae), commonly known as "ginkgo", is called a living fossil, and it has been cultivated early in human history for various uses in traditional medicine and as a source of food. As part of ongoing research to explore the chemical diversity and biologically active compounds from natural resources, two new coumaric acid-aliphatic alcohol hybrids, ginkwanghols A (1) and B (2) were isolated from the leaves of G. biloba. The coumaric acid-aliphatic alcohol hybrids of natural products have rarely been reported. The structures of the new compounds were determined by extensive NMR spectroscopic analysis, HRESI-MS, and quantum chemical ECD calculations, and by comparing the experimental HRESI-MS/MS spectrum of chemically transformed compound 1a with the predicted HRESI-MS/MS spectra proposed from CFM-ID 3.0, a software tool for MS/MS spectral prediction and MS-based compound identification. Ginkwanghols A (1) and B (2) increased alkaline phosphatase (ALP) production in C3H10T1/2, a mouse mesenchymal stem cell line, in a dose-dependent manner. In addition, ginkwanghols A and B mediated the promotion of osteogenic differentiation as indicated by the induction of the mRNA expression of the osteogenic markers ALP and osteopontin (OPN).