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BACKGROUND: Aspergillus infection seriously jeopardizes the health and safety of life of immunocompromised patients. The emergences of antifungal resistance highlight a demand to find new effective antifungal drugs. Angelica sinensis is a medicine–food herb and phthalides are its characteristic components. A few of the phthalides have been reported to display satisfactory antifungal activities against plant pathogenic fungi. However, the structure–activity relationships and antifungal action mechanism of phthalides remain to be further explored and elucidated. RESULTS: The antifungal activities of five natural phthalides and four artificial analogs were investigated, and their structure–activity relationships were preliminarily elucidated in the current study. The benzene ring moiety played an essential role in their antifungal activities; the oxygen‐containing substituents on the benzene ring obviously impacted their activities, the free hydroxyl was favorable to the activity. Typical phthalide senkyunolide B (SENB) exhibited broad antifungal activities against human and plant pathogenic fungi, especially, Aspergillus fumigatus. SENB affected the spore germination and hyphae growth of Aspergillus fumigatus via down‐regulating phosphatidylinositol‐PKC‐calcineurin axis and the expression of ENG genes. Moreover, SENB disturbed the oxidation–reduction process in Aspergillus fumigatus to destroy the mature biofilms. In vivo experiments indicated SENB significantly prolonged survival and decreased fungal burden in mouse model of invasive pulmonary aspergillosis. CONCLUSIONS: Phthalides could be considered as the valuable leads for the development of antifungal drug to cure plant and human disease. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of Fufang Huangqi Decoction on the gut microbiota in patients with class I or II myasthenia gravis (MG) and to explore the correlation between gut microbiota and MG (registration number, ChiCTR2100048367; registration website, http://www.chictr.org.cn/listbycreater.aspx; NCBI: SRP338707). Methods: In this study, microbial community composition and diversity analyses were carried out on fecal specimens from MG patients who did not take Fufang Huangqi Decoction (control group, n = 8) and those who took Fufang Huangqi Decoction and achieved remarkable alleviation of symptoms (medication group, n = 8). The abundance, diversity within and between habitats, taxonomic differences and corresponding discrimination markers of gut microbiota in the control group and medicated group were assessed. Results: Compared with the control group, the medicated group showed a significantly decreased abundance of Bacteroidetes (P < 0.05) and significantly increased abundance of Actinobacteria at the phylum level, a significantly decreased abundance of Bacteroidaceae (P < 0.05) and significantly increased abundance of Bifidobacteriaceae at the family level and a significantly decreased abundance of Blautia and Bacteroides (P < 0.05) and significantly increased abundance of Bifidobacterium, Lactobacillus and Roseburia at the genus level. Compared to the control group, the medicated group had decreased abundance, diversity, and genetic diversity of the communities and increased coverage, but the differences were not significant (P > 0.05); the markers that differed significantly between communities at the genus level and influenced the differences between groups were Blautia, Bacteroides, Bifidobacterium and Lactobacillus. Conclusions: MG patients have obvious gut microbiota-associated metabolic disorders. Fufang Huangqi Decoction regulates the gut microbiota in patients with class I or II MG by reducing the abundance of Blautia and Bacteroides and increasing the abundance of Bifidobacterium and Lactobacillus. The correlation between gut microbiota and MG may be related to cell-mediated immunity. [ABSTRACT FROM AUTHOR]

Riligustilide (RG), one of the dimeric phthalides of Angelica sinensis and Ligusticum chuanxiong, was confirmed effective against many diseases. However, its effects on type 2 diabetes mellitus (T2DM) and the underlying molecular mechanisms have not been clearly elucidated yet. The current study was designed to investigate the hypoglycemic potential by which RG affects the pathogenesis of T2DM. Comprehensive insights into the effects and underlying molecular mechanisms of RG on attenuating aberrant metabolism of glucose were determined in high-fat diet-induced T2DM mice and insulin-resistant (IR) HepG2 cells. In high-fat diet-induced C57BL/6J mice, RG administration significantly reduced hyperglycemia, decreased hyperinsulinemia, and ameliorated glucose intolerance. Mechanistically, RG activated PPARγ and insulin signaling pathway to improve insulin sensitivity, and increase glucose uptake as well as glycogenesis. In addition, RG also upregulated AMPK-TORC2-FoxO1 axis to attenuate gluconeogenesis in vivo and in vitro. According to the findings, RG may be a promising candidate for the treatment of T2DM. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease characterized by β-amyloid (Aβ) protein deposition, neurofibrillary tangle (NFT) formation, and neuronal loss in the brain. The current study was designed to investigate the potential mechanisms by which levistolide A affects the pathogenesis of AD in an amyloid precursor protein/presenilin 1 (APP/PS1) transgenic (Tg) mouse model of AD and N2a/APP695swe cells. Specifically, behavioral changes in levistolide A–treated APP/PS1 Tg mice were assessed by the nest-building and Morris water maze (MWM) tests. Levistolide A treatment clearly ameliorated memory deficits and cognitive decline in APP/PS1 Tg mice. Aβ generation and the inflammatory response in APP/PS1 Tg mouse brains were clearly reduced after long-term levistolide A application. Mechanistically, levistolide A concurrently stimulated the expression of α-secretase and decreased the generation of β- and γ-secretases. In addition, levistolide A inhibited the phosphorylation of tau in the brains of the Tg mice. Furthermore, in vitro and in vivo experiments suggested that peroxisome proliferator–activated receptor γ (PPARγ) is the key transcription factor that mediates the regulatory effects of levistolide A on the expression of α-, β-, and γ-secretases and phosphorylation of tau. Collectively, these findings show that levistolide A may be a candidate for the treatment of AD. [ABSTRACT FROM AUTHOR]

In the process of investigating the antifungal structure-activity relationships (SAR) of borrelidin and discovering antifungal leads, a semisynthetic borrelidin analogue, BN-3b with antifungal activity against Candida albicans, was achieved. In this study, we found that oxidative damage induced by endogenous reactive oxygen species (ROS) plays an important role in the antifungal activity of BN-3b. Further investigation indicated that BN-3b stimulated ROS accumulation, increased malondialdehyde (MDA) levels, and decreased reduced/oxidized glutathione (GSH/GSSG) ratio. Moreover, BN-3b decreased mitochondrial membrane potential (MMP) and ATP generation. Ultrastructure analysis revealed that BN-3b severely damaged the cell membrane of C. albicans. Quantitative PCR (RT-qPCR) analysis revealed that virulence factors of C. albicans SAPs, PLB1, PLB2, HWP1, ALSs, and LIPs were all down-regulated after BN-3b exposure. We also found that BN-3b markedly inhibited the hyphal formation of C. albicans. In addition, in vivo studies revealed that BN-3b significantly prolonged survival and decreased fungal burden in mouse model of disseminated candidiasis. [ABSTRACT FROM AUTHOR]

In addition to the SP 13 sp C NMR signals corresponding with the SP 1 sp H NMR data, one ester carbonyl at I i SB C sb 177.4 and one sp SP 3 sp nonprotonated carbon at I i SB C sb 69.2 were observed. The oxymethylene protons of C-5 for the ( I R i )-MTPA ester were observed as separated double doublet signals at I i SB H sb 4.53 and I i SB H sb 4.30 ( I i 0.23), whereas those for the ( I S i )-MTPA ester appeared as multiplet signals at I i SB H sb 4.42 and I i SB H sb 4.40 ( I i 0.02). NMR spectra ( SP 1 sp H NMR, SP 13 sp C NMR, s, HSQC, HMBC, and NOESY) were acquired on a Bruker 600 MHZ AVIII HD operating at 600.13 and 150.90 MHz for SP 1 sp H and SP 13 sp C, respectively. GRAPH: Figure S1. 1H NMR (600 MHz, DMSO-d6) spectrum of the new compound 1Figure S2. 1H NMR (600 MHz, CDCl3) spectrum of the new compound 1Figure S3. 13C NMR (150 MHz, DMSO-d6) spectrum of the new compound 1Figure S4. [Extracted from the article]