Chang-Kang-Fang alleviates diarrhea predominant irritable bowel syndrome (IBS-D) through inhibiting TLR4/NF-κB/NLRP3 pathway.

Ethnopharmacological Relevance: Chang-Kang-Fang (CKF), originated from traditional Chinese medicine (TCM) formulas, has been utilized to treat diarrhea predominant irritable bowel syndrome (IBS-D) based on clinical experience. However, the underlying mechanism of CKF for treating IBS-D remains unclear and need further clarification.

Aim Of The Study: The objective of this present investigation was to validate the efficacy of CKF on IBS-D model rats and to uncover its potential mechanism for the treatment of IBS-D.

Novel citrinin derivatives from fungus Penicillium sp. TW131-64 and their antimicrobial activities.

Six new citrinin derivatives (1, 2, 4, 10, 11, and 16), along with fourteen known analogues, were acquired from Penicillium sp. TW131-64, a marine-derived fungus strain. The chemical structures of new compounds were identified through adopting various spectroscopic methods in combination with X-ray diffraction technology and comparison of the experimental electronic circular dichroism (ECD) with calculated ones.

Deciphering chemical and metabolite profiling of Chang-Kang-Fang by UPLC-Q-TOF-MS/MS and its potential active components identification.

Chang-Kang-Fang (CKF) formula, a Traditional Chinese Medicine (TCM) prescription, has been widely used for the treatment of irritable bowel syndrome (IBS). However, its potential material basis and underlying mechanism remain elusive. Therefore, this study employed an integrated approach that combined ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) with network pharmacology to systematically characterize the phytochemical components and metabolites of CKF, as well as elucidating its underlying mechanism.

Molecular Networking-Guided Isolation of Cyclopentapeptides from the Hydrothermal Vent Sediment Derived Fungus TW58-5 and Their Anti-inflammatory Effects.

Repetitive isolation of known compounds remains a major challenge in natural-product-based drug discovery. LC-MS/MS-based molecular networking has become a highly efficient strategy for the discovery of new natural products from complex mixtures. Herein, we report a molecular networking-guided isolation procedure, which resulted in the discovery of seven new cyclopentapeptides, namely, pseudoviridinutans A-F (-), from the marine-derived fungus TW58-5.

Deciphering in vivo metabolic profile and pharmacological mechanisms of Jitongning Tablet for the treatment of Ankylosing spondylitis.

Jitongning tablet (JTNT) is a Traditional Chinese Medicine (TCM) prescription used for the treatment of Ankylosing spondylitis (AS). Currently, it is in phase II clinical trial (NCT03932019) for patients with active axial Spondyloarthritis (axSpA), showing great promise for the treatment of AS. However, the potential material basis and the underlying mechanisms for JTNT to treat AS remain elusive.

New Polyketides from a Hydrothermal Vent Sediment Fungus sp. JWM29-10-1 and Their Antimicrobial Effects.

Marine fungi-derived secondary metabolites are still an important source for the discovery of potential antimicrobial agents. Here, five new polyketides (, , and -) and seven known compounds (- and -) were obtained from the culture of the marine-derived fungus sp. JWM29-10-1.

Naphthoquinones and triterpenoids from Arnebia euchroma (Royle) Johnst and their hypoglycemic and lipid-lowering effects.

A new pentacyclic triterpenoid, 2-hydroxy-1-ene-hydroxyhopanone (19), and a new benzoxepin-5-one, 3-(4-methyl-3-penten-1-yl)-6-hydroxy-9-methoxy-2H-1-benzoxepin-5-one (25), along with 26 known compounds (1-18, 20-24, 26-28), were isolated from the roots of Arnebia euchroma (Royle) Johnst. The structures of the new compounds were elucidated by extensive spectroscopic analyses. The absolute configurations of shikonofurans 9-13 were determined by quantum chemical ECD calculations and CD spectra comparison for the first time.

Chemical screen identifies shikonin as a broad DNA damage response inhibitor that enhances chemotherapy through inhibiting ATM and ATR.

DNA damage response (DDR) is a highly conserved genome surveillance mechanism that preserves cell viability in the presence of chemotherapeutic drugs. Hence, small molecules that inhibit DDR are expected to enhance the anti-cancer effect of chemotherapy. Through a recent chemical library screen, we identified shikonin as an inhibitor that strongly suppressed DDR activated by various chemotherapeutic drugs in cancer cell lines derived from different origins.

Synthesis of sorbicillinoid analogues with anti-inflammation activities.

Recently, we demonstrated potential anti-inflammatory effects of sorbicillinoids isolated from marine fungi. Here, we report the synthesis of a series of new sorbicillinoid analogues and assessed their anti-inflammatory activities. Our results reveal that side chain substitution with (E)-2-butenoyl, (E)-3-(4-fluorophenyl)-2-propenoyl, and (E)-3-(3,4,5-trimethoxyphenyl)-2-propenoyl significantly enhanced the inhibitory effects of the derivatives on nitric oxide (NO) production and inducible NO synthesis (iNOS) expression stimulated by lipopolysaccharides (LPS) in mouse macrophage.

New diketopiperazine alkaloid and polyketides from marine-derived fungus Penicillium sp. TW58-16 with antibacterial activity against Helicobacter pylori.

Marine-derived fungi can usually produce structurally novel and biologically potent metabolites. In this study, a new diketopiperazine alkaloid (1) and two new polyketides (10 and 11), along with 8 known diketopiperazine alkaloids (2-9) were isolated from marine-derived fungus Penicillium sp. TW58-16.

New Drimane Sesquiterpenes and Polyketides from Marine-Derived Fungus sp. TW58-16 and Their Anti-Inflammatory and -Glucosidase Inhibitory Effects.

Marine fungi-derived natural products represent an excellent reservoir for the discovery of novel lead compounds with biological activities. Here, we report the identification of two new drimane sesquiterpenes ( and ) and six new polyketides (-), together with 10 known compounds (-), from a marine-derived fungus sp. TW58-16.

Isolation and Characterization of Anti-Inflammatory Sorbicillinoids from the Mangrove-Derived Fungus Penicillium sp. DM815.

Marine derived fungus has gained increasing ground in the discovery of novel lead compounds with potent biological activities including anti-inflammation. Here, we first report the characterization of one new sorbicillinoid (1) and fourteen known compounds (2-15) from the ethyl acetate (AcOEt) extract of a cultured mangrove derived fungus Penicillium sp. DM815 by UV, IR, HR ESI-Q-TOF MS, and NMR spectra.

Benzannulated 5,5-spiroketal sesquiterpenes from the roots of Angelica Pubescens.

Two new tetrahydrobenzannulated 5,5-spiroketal sesquiterpenes (1 and 2) and three novel benzannulated 5,5-spiroketal sesquiterpenes (3-5) namely angepubesins A-E, together with a new heliannane-type benzannulated sesquiterpene namely angepubesin F (6) and two known monoterpenes (7 and 8), were isolated from the roots of Angelica Pubescens. Their structures were identified by various spectroscopic analyses (NMR, MS, UV, IR), in combination with C NMR calculation as well as MAE, CMAE, DP4 + and MAE values analyses. The absolute configurations of 1-6 were determined by modified Mosher's method, ECD calculation and single-crystal X-ray diffraction (Cu Kα).

New Ophiobolins from the Deep-Sea Derived Fungus sp. WHU0154 and Their Anti-Inflammatory Effects.

Deep-sea fungi have become a new arsenal for the discovery of leading compounds. Here five new ophiobolins -, together with six known analogues -, obtained from a deep-sea derived fungus WHU0154. Their structures were determined by analyses of IR, HR-ESI-MS, and NMR spectra, along with experimental and calculated electronic circular dichroism (ECD) analysis.

Cardiac glycosides inhibit cancer through Na/K-ATPase-dependent cell death induction.

Successful drug repurposing relies on the understanding of molecular mechanisms of the target compound. Cardiac glycosides have demonstrated potent anticancer activities; however, the pharmacological mechanisms underlying their anticancer effects remained elusive, which has restricted their further development in cancer treatment. A bottleneck is the lack of comprehensive understanding about genes and signaling pathways that are altered at the early stage of drug treatment, which is key to understand how they inhibit cancer.

Targeting UHRF1-dependent DNA repair selectively sensitizes KRAS mutant lung cancer to chemotherapy.

Kirsten rat sarcoma virus oncogene homolog (KRAS) mutant lung cancer remains a challenge to cure and chemotherapy is the current standard treatment in the clinic. Hence, understanding molecular mechanisms underlying the sensitivity of KRAS mutant lung cancer to chemotherapy could help uncover unique strategies to treat this disease. Here we report a compound library screen and identification of cardiac glycosides as agents that selectively enhance the in vitro and in vivo effects of chemotherapy on KRAS mutant lung cancer.

Corrigendum: Shikonin Inhibits Cancer Through P21 Upregulation and Apoptosis Induction.

[This corrects the article DOI: 10.3389/fphar.2020.

New pyrones and their analogs from the marine mangrove-derived Aspergillus sp. DM94 with antibacterial activity against Helicobacter pylori.

Marine fungi are well known for their ability to produce a multitude of natural products and have been proved to be a particularly rich source of drug leads. Here, 20 pyrones and their analogs (1-20), including two new compounds (1 and 6), were obtained from a marine-derived fungus strain of Aspergillus sp. DM94.

Shikonin Inhibits Cancer Through P21 Upregulation and Apoptosis Induction.

Shikonin is a natural naphthoquinone compound and has demonstrated potent anti-cancer activities; however, the underlying molecular mechanisms remained elusive. Here we report that Shikonin inhibited the growth of a wide range of human cancer cell lines, illustrating a broad anticancer effect. Mechanistically, we show that Shikonin arrested the cell cycle at the G2/M phase, inhibited the ERK-dependent cell growth signal, and induced cell death in both P53 wild type and mutant cancer cells, which collectively contributed to the growth inhibitory effect of Shikonin.

Author Correction: Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Prenylated benzenepropanoic acid analogues from the Citrus grandis (L.) Osbeck and their anti-neuroinflammatory activity.

Phytochemical studies of the air-dried pericarp of Citrus grandis led to the isolation of four new compounds including three prenylated benzenepropanoic acids (2, 3 and 5) and one alkamidic glycoside (6), together with ten known compounds (1, 4 and 7-14). The structures of these compounds were determined by the NMR spectroscopy, optical rotation data and modified Mosher's method. Meanwhile, the anti-neuroinflammatory activities of all isolated compounds were evaluated by detecting the production of nitric oxide (NO) in LPS-stimulated BV2 cells.

Coumarin Analogues from the Citrus grandis (L.) Osbeck and Their Hepatoprotective Activity.

Seven new coumarin analogues (1, 2, and 4-8), together with ten known analogues (3, 9-17), were isolated from the air-dried pericarp of Citrus grandis. The structures of these compounds were determined by HR-ESI-MS, UV/vis, and 1D- and 2D-NMR spectra. Meanwhile, the hepatoprotective activities of all these coumarins were evaluated by MTT assays using the d-galactosamine-induced LO2 cell injury model.

Design and synthesis of biotinylated cardiac glycosides for probing Nur77 protein inducting pathway.

The orphan nuclear receptor Nur77 (also known as TR3 or nerve growth factor-induced clone B NGFI-B) functions as a nuclear transcription factor in the regulation of target gene expression and plays a critical role in the regulation of differentiation, proliferation, apoptosis, and survival of many different cell types. Recent studies demonstrate that Nur77 also involves many important physiological and pathological processes including cancer, inflammation and immunity, cardiovascular diseases, and bone diseases. Our previous studies showed that cardiac glycosides could induce the expression of Nur77 protein and its translocation from the nucleus to the cytoplasm and subsequent targeting to mitochondria, leading to apoptosis of cancer cells.

Harmines inhibit cancer cell growth through coordinated activation of apoptosis and inhibition of autophagy.

Harmine and its analogs have long been considered as anticancer agents. In vitro analyses suggested that intercalating DNA or inhibiting topoisomerase might contribute to the cytotoxic effect of this class of compound. However, this idea has not been rigorously tested in intact cells.