Five undescribed meroterpenoids from Ganoderma lucidum and their inhibitory activities against renal fibrosis.

Five undescribed meroterpenoids, baosglucidnes A - E (1-5), were isolated from the fruiting bodies of Ganoderma lucidum. Among them, baosglucidne B (2) as a racemic mixture was obtained. Chiral HPLC was employed to separate a pair of enantiomers (+)-2 and (-)-2. The structures and stereochemical features of these substances were characterized by utilizing spectroscopic data and ECD calculations. Finally, the results of anti-renal fibrosis activity evaluation showed that baosglucidne E (5) could inhibit the expression of collagen I in TGF-ß1-induced rat kidney proximal tubular cells at 20 µM.

Medicinal plant resin natural products: structural diversity and biological activities.

Covering: up to the mid of 2023Plants secrete defense resins rich in small-molecule natural products under abiotic and biotic stresses. This comprehensive review encompasses the literature published up to mid-2023 on medicinal plant resin natural products from six main contributor genera, featuring 275 citations that refer to 1115 structurally diverse compounds. The scope of this review extends to include essential information such as the racemic nature of metabolites found in different species of plant resins, source of resins, and revised structures. Additionally, we carefully analyze the reported biological activities of resins, organizing them based on the their structures. The findings offer important insights into the relationship between their structure and activity. Furthermore, this detailed examination can be valuable for researchers and scientists in the field of medicinal plant resin natural products and will promote continued exploration and progress in this area.

Investigation of the Inhibitory Effects of Illicium verum Essential Oil Nanoemulsion on Fusarium proliferatum via Combined Transcriptomics and Metabolomics Analysis.

Fusarium proliferatum is the main pathogen that causes Panax notoginseng root rot. The shortcomings of strong volatility and poor water solubility of Illicium verum essential oil (EO) limit its utilization. In this study, we prepared traditional emulsion (BDT) and nanoemulsion (Bneo) of I. verum EO by ultrasonic method with Tween-80 and absolute ethanol as solvents. The chemical components of EO, BDT, and Bneo were identified by gas chromatography-mass spectrometry (GC-MS) and the antifungal activity and mechanism were compared. The results show that Bneo has good stability and its particle size is 34.86 nm. The contents of (-) -anethole and estragole in Bneo were significantly higher than those in BDT. The antifungal activity against F. proliferatum was 5.8-fold higher than BDT. In the presence of I. verum EO, the occurrence of P. notoginseng root rot was significantly reduced. By combining transcriptome and metabolomics analysis, I. verum EO was found to be involved in the mutual transformation of pentose and glucuronic acid, galactose metabolism, streptomycin biosynthesis, carbon metabolism, and other metabolic pathways of F. proliferatum, and it interfered with the normal growth of F. proliferatum to exert antifungal effects. This study provide a theoretical basis for expanding the practical application of Bneo.

Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans.

Twelve new alkaloids, scolopenolines A-L (1-7, 9-11, 13, 14), along with six known analogues, were isolated from Scolopendra subspinipes mutilans, identified by analysis of spectroscopic data and quantum chemical and computational methods. Scolopenoline A (1), a unique guanidyl-containing C14 quinoline alkaloid, features a 6/6/5 ring backbone. Scolopenoline B (2) is a novel sulfonyl-containing heterodimer comprising quinoline and tyramine moieties. Scolopenoline G (7) presents a rare C12 quinoline skeleton with a 6/6/5 ring system. Alkaloids 1, 8, 10, and 15-18 display anti-inflammatory activity, while 10 and 16-18 also exhibit anti-renal-fibrosis activity. Drug affinity responsive target stability and RNA-interference assays show that Lamp2 might be a potentially important target protein of 16 for anti-renal-fibrosis activity.

Five undescribed cyclopeptides from Cordyceps militaris.

Ustiloxins I-M (1-5), five undescribed cyclopeptides bearing a 15-membered macrocyclic skeleton, were isolated from Cordyceps militaris. The structures of 1 and 5 were identified by spectroscopic and crystallographic methods, whereas the structures of 2-4 were assigned by spectroscopic and computational approaches. Biological evaluation of all the compounds toward human triple-negative breast cancer cells revealed that compounds 4 and 5 are toxic with IC50 values of 64.29 µM and 28.89 µM, respectively.

Ganoderma lucidum-Derived Meroterpenoids Show Anti-Inflammatory Activity In Vitro.

Ganoderma lucidum, known as the "herb of spiritual potency", is used for the treatment and prevention of various diseases, but the responsible constituents for its therapeutic effects are largely unknown. For the purpose of obtaining insight into the chemical and biological profiling of meroterpenoids in G. lucidum, various chromatographic approaches were utilized for the title fungus. As a result, six undescribed meroterpenoids, chizhienes A-F (1-6), containing two pairs of enantiomers (4 and 5), were isolated. Their structures were identified using spectroscopic and computational methods. In addition, the anti-inflammatory activities of all the isolates were evaluated by Western blot analysis in LPS-induced macrophage cells (RAW264.7), showing that 1 and 3 could dose dependently inhibit iNOS but not COX-2 expression. Further, 1 and 3 were found to inhibit nitric oxide (NO) production using the Greiss reagent test. The current study will aid in enriching the structural and biological diversity of Ganoderma-derived meroterpenoids.

Minor ergosteroids and a 19-nor labdane-type diterpenoid with anti-inflammatory effects from Ganoderma lucidum.

A chemical investigation on the fruiting bodies of Ganoderma lucidum led to the isolation and identification of five undescribed ergosteroids including two des-D-steroids (3 and 4) and one rare 6/6/7/5-fused carbon skeletal ergosterol (5) along with one 19-nor labdane-type diterpenoid (6). Their structures including their absolute configurations, were assigned by spectroscopic methods, ECD calculations, and X-ray diffraction analysis. In addition, the anti-inflammatory activities of all the isolates were evaluated. The results indicated that compound 1 can significantly down-regulate the protein expression of iNOS and COX-2 at 20 µM in LPS- stimulated RAW264.7 cells.

Mantidisflavin A: A Riboflavin Derivative Featuring a 6/6/6/5/5 Skeleton from the Egg Cases of the Insect Tenodera sinensis Saussure and Its Anti-Renal Fibrosis Activity.

Mantidisflavin A (1) was isolated from the egg cases of the Tenodera sinensis Saussure. It exhibits an unprecedented 6/6/6/5/5 skeleton, accompanied by the formation of two additional fused heterocycles through a novel C-C bond and an oxygen bridge on riboflavin backbone. The structure of 1 was identified by spectroscopic and computational methods. To assess the inhibitory effect against renal fibrosis, compound 1 was evaluated in TGF-ß1-induced rat kidney epithelial cells, and the results were compared to those of its precursor, riboflavin.

Aspongopyrimidine A, a N-Peralkylated Histidine Zwitterion from Aspongopus chinensis against Alzheimer's Disease Targeting MAPRE3.

Aspongopyrimidine A (1), a hexa-1,3-diene-histidine-hexanoic acid adduct featuring a 4,5-dihydro-2H-10λ4-imidazo[5,1-f]pyrrolo[2,1-b]pyrimidine motif, was isolated from the insect Aspongopus chinensis. The structure was clarified by spectroscopic and computational methods and X-ray diffraction. Peralkylation of N-atoms in histidine by two C6 units makes 1 an inner salt with a 5/6/5 tricyclic system. Biological evaluation found that 1 exerts activity against Alzheimer's disease targeting MAPRE3 through a chemical proteomics approach. This study revealed unusual modifications of amino acids as the fundamental units of protein.

A naturally derived small molecule compound suppresses tumor growth and metastasis in mice by relieving p53-dependent repression of CDK2/Rb signaling and the Snail-driven EMT.

The tumor suppressor protein p53 is central to cancer biology, with its pathway reactivation emerging as a promising therapeutic strategy in oncology. This study introduced LZ22, a novel compound that selectively inhibits the growth, migration, and metastasis of tumor cells expressing wild-type p53, demonstrating ineffectiveness in cells devoid of p53 or those expressing mutant p53. LZ22's mechanism of action involves a high-affinity interaction with the histidine-96 pocket of the MDM2 protein. This interaction disrupted the MDM2-p53 binding, consequently stabilizing p53 by shielding it from proteasomal degradation. LZ22 impeded cell cycle progression and diminished cell proliferation by reinstating the p53-dependent suppression of the CDK2/Rb signaling pathway. Moreover, LZ22 alleviated the p53-dependent repression of Snail transcription factor expression and its consequent EMT, effectively reducing tumor cell migration and distal metastasis. Importantly, LZ22 administration in tumor-bearing mice did not manifest notable side effects. The findings position LZ22 as a structurally unique reactivator of p53, offering therapeutic promise for the management of human cancers with wild-type TP53.

Isolation and target identification of anti-renal fibrosis compounds from Cordyceps militaris.

Four undescribed compounds including one aromatic glucoside derivative, cordyceglycoside A (1), one new isoleucine derivative inner salt, cordycepisosalt A (2), a rare four-membered lactam, cinerealactam B (3), and one sesquiterpene derivative, cordycepsetp A (4), together with six known compounds were isolated from Cordyceps militaris. The structures including absolute configurations of these new compounds, were unambiguously elucidated by spectroscopic data analysis and single crystal X-ray diffraction. Biological evaluation of compounds 1-4 showed that 3 displays anti-renal fibrotic activities in TGF-ß1 induced NRK-52e cells. Furthermore, DARTS coupled with LC-MS/MS analysis was used to identify candidate target proteins for 3. Subsequently, C1qbp knockdown using siRNA allowed us to validate the target protein of 3.

Insights into Ganoderma fungi meroterpenoids opening a new era of racemic natural products in mushrooms.

Ganoderma meroterpenoids (GMs) containing 688 structures to date were discovered to have multiple remarkable biological activities. 65.6% of meroterpenoids featuring stereogenic centers from Ganoderma species are racemates. Further, GMs from different Ganoderma species seem to have their own characteristics. In this review, a comprehensive summarization of GMs since 2000 is presented, including GM structures, structure corrections, biological activities, physicochemical properties, total synthesis, and proposed biosynthetic pathways. Additionally, we especially discuss the racemic nature, species-related structural distribution, and structure-activity relationship of GMs, which will provide a likely in-house database and shed light on future studies on GMs.

Dimeric diarylheptanoids with anti-inflammatory activity from Zingiber officinale.

Two previously undescribed chain diarylheptanoid derivatives (2-3), five previously undescribed dimeric diarylheptanoids (4-8), together with one known cyclic diarylheptanoid (1) were isolated from Zingiber officinale. Their structures were elucidated by extensive spectroscopic analyses (HR-ESI-MS, IR, UV, 1D and 2D NMR) and ECD calculations. Biological evaluation of compounds 1-8 revealed that compounds 2, 3 and 4 could inhibit nitrite oxide and IL-6 production in lipopolysaccharide induced RAW264.7 cells in a dose-dependent manner.

Identification of arnicolide C as a novel chemosensitizer to suppress mTOR/E2F1/FANCD2 axis in non-small cell lung cancer.

BACKGROUND AND PURPOSE: The mammalian target of rapamycin (mTOR) pathway plays critical roles in intrinsic chemoresistance by regulating Fanconi anaemia complementation group D2 (FANCD2) expression. However, the mechanisms by which mTOR regulates FANCD2 expression and related inhibitors are not clearly elucidated. Extracts of Centipeda minima (C. minima) showed promising chemosensitizing effects by inhibiting FANCD2 activity. Here, we have aimed to identify the bioactive chemosensitizer in C. minima extracts and elucidate its underlying mechanism. EXPERIMENTAL APPROACH: The chemosensitizing effects of arnicolide C (ArC), a bioactive compound in C. minima, on non-small cell lung cancer (NSCLC) were investigated using immunoblotting, immunofluorescence, flow cytometry, the comet assay, small interfering RNA (siRNA) transfection and animal models. The online SynergyFinder software was used to determine the synergistic effects of ArC and chemotherapeutic drugs on NSCLC cells. KEY RESULTS: ArC had synergistic cytotoxic effects with DNA cross-linking drugs such as cisplatin and mitomycin C in NSCLC cells. ArC treatment markedly decreased FANCD2 expression in NSCLC cells, thus attenuating cisplatin-induced FANCD2 nuclear foci formation, leading to DNA damage and apoptosis. ArC inhibited the mTOR pathway and attenuated mTOR-mediated expression of E2F1, a critical transcription factor of FANCD2. Co-administration of ArC and cisplatin exerted synergistic anticancer effects in the A549 xenograft mouse model by suppressing mTOR/FANCD2 signalling in tumour tissues. CONCLUSION AND IMPLICATIONS: ArC suppressed DNA cross-linking drug-induced DNA damage response by inhibiting the mTOR/E2F1/FANCD2 signalling axis, serving as a chemosensitizing agent. This provides insight into the anticancer mechanisms of ArC and offers a potential combinatorial anticancer therapeutic strategy.

N-containing phenolic compounds from Periplaneta americana with triple negative breast cancer inhibitory activity.

Eight previously undescribed compounds comprising pyrrole-2-carboxaldehyde derivatives, namely periplanpyrroles A-D (1-4), spirooxindole derivatives perispirooxindoles A (5) and B (6), and the phenolic compounds periplanetols G (7) and H (8), along with eight known compounds were isolated from the 70% ethanol extract of the whole bodies of Periplaneta americana. Their structures including absolute configurations were unambiguously identified by comprehensive spectroscopic analyses and computational methods. In addition, all compounds were evaluated for their activities against triple negative breast cancer in vitro. The wound healing assay revealed that 7, 9, and 11 significantly inhibit the migration of BT549 and MDA-MB-231 cells. Further observations made in Western blotting experiments showed that 7 could dose-dependently decrease the protein level of vimentin and N-cadherin in MDA-MB-231 and BT549 cells.

Dimeric N-Acetyldopamine Derivatives Featuring a Seco-Benzene System from the Insects Aspongopus chinensis and Periostracum cicadae.

Aspongamide F (1), a novel N-acetyldopamine (NADA) dimer possessing a 6/6/6 ring system, and (±)-aspongamides G (2) and H (3), rare NADA derivatives with fragmented benzene rings, were isolated from Aspongopus chinensis. (±)-Cicadamides C (4) and D (5), the first 1,4-Benzodioxane NADA dimers featuring a seco-benzene system, and (±)-cicadamides E (6) and F (7), the NADA dimers derivatives, were isolated from Periostracum cicadae. The structures of all compounds were elucidated by spectroscopic analyses and computational methods. A plausible biosynthetic pathway for compounds 1-5 was proposed. The biological assay revealed that (+)-4 and (-)-4 exhibit renal protection in a dose-dependent manner.

Molecular Insights into the Salinity Effects on Movability of Oil-Brine in Shale Nanopore-Throat Systems.

Low-salinity flooding has been well recognized as a promising strategy to increase shale oil recovery, but the underlying mechanism remains unclarified, especially for complex nanopore networks filled with oil-brine fluids. In this study, the pressure-driven flow of an oil-brine fluid with varying salinities in shale nanopore-throat channels was first investigated based on molecular dynamics simulations. The critical pressure driving oil to intrude into a nanothroat filled with brine of varying salinities was determined. Simulation results indicate that the salinity of brine exhibits great effects on the movability of oil, and low salinity favors the increase of oil movability. Further analysis of the interactions between fluid and pore walls as well as the displacement pressures reveals dual effects of brine salinity on oil transportation in a nanopore-throat. On the one hand, hydrated cations anchoring onto throat walls enlarge the effective flow width in the throat before the hydration complexes reach the maximum. On the other hand, the interfacial tension between oil and brine increases with the brine salinity, which increases the capillary resistance and leads to a higher displacement pressure. These findings highlight the effects of brine salinity on oil movability in a nanopore-throat, which will promote the understanding of oil accumulation and dissipation in petroleum systems, as well as help to develop enhanced oil recovery.

Novel spirooxindole alkaloid derivatives from the medicinal insect Blaps japanensis and their biological evaluation.

Blapspirooxindoles A-C (1-3), three novel spirooxindole alkaloids with a unique spiro[chromane-4,3'-indoline]-2,2'-dione motif, blapcumaranons A and B (4 and 5), two new 2-cumaranon derivatives, blapoxindoles A-J (6-15), ten new oxindole alkaloid derivatives, along with one known compound (16), were isolated from the whole bodies of Blaps japanensis. Their structures including absolute configurations were determined by using spectroscopic, X-ray crystallographic, and computational methods. Compounds 1-11 and 13 exist as racemic mixtures in nature, and their (-)- and (+)-antipodes were separated by chiral HPLC. Biological evaluations of these compounds were determined with multiple assays including anti-tumor, anti-inflammatory, and renal protection activities in vitro. Several compounds displayed effective activity in one or more assays.

Renoprotective Glycoside Derivatives from Zingiber officinale (Ginger) Peels.

As a widely consumed spice and traditional Chinese medicine, Zingiber officinale Roscoe (ginger) has been used in the treatment of nausea, coughs, and colds. In this article, 18 new glycosides (1-18) and six known analogues (19-24) were isolated from the peel of ginger. The planar structures of these compounds were determined by using HR-ESI-MS and extensive spectroscopic techniques (UV, IR, 1D-NMR, and 2D-NMR). Their relative and absolute configurations of the stereogenic centers in the new natural products were determined by analysis of NMR data, using a quantum mechanical NMR approach and time-dependent density functional theory based electronic circular dichroism calculations. The renal fibrosis activities of the isolated natural products together with those of 6-gingerol (6-Gi), 8-gingerol (8-Gi), and 10-gingerol (10-Gi) were evaluated in TGF-ß1 induced NRK-52E cells. Compounds 9, 10, 15, 22-24, 6-Gi, 8-Gi, and 10-Gi were found to be active toward extracellular matrix, indicating that they have potential renal fibrosis activities.

Design and synthesis of photoaffinity-based probes for labeling ß-glucuronidase.

ß-Glucuronidase (GUSB) plays an important role in human physiological and pathological activities. The activity level of GUSB is closely related to human health and diseases. It is imperative to detect the activity of GUSB for related disease diagnosis and treatment. However, exactly evaluating the activity of GUSB in complicated biological system remains a challenge. In this study, we developed photoaffinity-based probes (AfBPs) equipped with photosensitive benzophenone group for labeling active GUSB. Through molecule docking, we predicted the binding model of the AfBPs and GUSB, and the obtained results suggested thermodynamically favorable binding. The AfBPs indicated high efficiency and showed dose-/time-dependent labeling of Escherichia coli (E. coli) GUSB. The application of AfBPs toward GUSB provides a powerful tool to study the activity of target enzymes and contributes to huge potential of enzyme inhibitor discovery and biomedical diagnostics.