Neuroprotective effects of torularhodin against H2O2-induced oxidative injury and apoptosis in PC12 cells.

The neuroprotective effects of torularhodin against oxidative injury and apoptosis in PC12 cells, as well as the related mechanisms, were investigated. The results showed that torularhodin significantly reduced lactate dehydrogenase (LDH) release and malondialdehyde (MDA) production, meanwhile increased the activities of antioxidant enzymes, which were assessed by enzyme linked immunosorbent assay. The presence of torularhodin attenuated H2O2-induced apoptosis which was proven by flow cytometric detection of Ca2+ influx inhibition and the mitochondrial membrane potential (MMP) reduction. Furthermore, the oxidative injury produced by H2O2 was mitigated by torularhodin pretreatment via down-regulation of GSK-3ß and Keap1 genes while up-regulating the expressions of Nrf2, HO-1 and NQO1 genes. The neuroprotective effects of torularhodin against oxidative injury and apoptosis appeared to be associated with the synergistic effect of mitochondria-mediated pathway and GSK-3ß/ Nrf2 signaling pathway. These findings demonstrated that torularhodin could be considered as a neuroprotective agent against H2O2-induced oxidative stress.

Neuroprotection of chicoric acid in a mouse model of Parkinson's disease involves gut microbiota and TLR4 signaling pathway.

Chicoric acid (CA), a polyphenolic acid obtained from chicory and purple coneflower (Echinacea purpurea), has been regarded as a nutraceutical to combat inflammation, viruses and obesity. Parkinson's disease (PD) is a common neurodegenerative disorder, and the microbiota-gut-brain axis might be the potential mechanism in the pathogenesis and development of PD. The results obtained in this study demonstrated that oral pretreatments of CA significantly prevented the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor dysfunctions and death of nigrostriatal dopaminergic neurons along with the inhibition of glial hyperactivation and the increment in striatal neurotrophins. 16S rRNA sequence results showed that CA significantly reduced MPTP-induced microbial dysbiosis and partially restored the composition of the gut microbiota to normal, including decreased phylum Bacteroidetes and genera Parabacteroide, as well as increased phylum Firmicutes, genera Lactobacillus and Ruminiclostridium. Besides, CA promoted colonic epithelial integrity and restored normal SCFA production. We also observed that proinflammatory cytokines such as TNF-α and IL-1ß in the serum, striatum and colon were reduced by CA, indicating that CA prevented neuroinflammation and gut inflammation, in which the suppression of the TLR4/MyD88/NF-κB signaling pathway might be the underlying molecular mechanism. These findings demonstrated that CA had neuroprotective effects on MPTP-induced PD mice possibly via modulating the gut microbiota and inhibiting inflammation throughout the brain-gut axis.

Development of UPLC-MS/MS method for determining hainanmycin in foods of animal origin.

Hainanmycin is a polyether antibiotic. Toxicological studies have shown the adverse effects of hainanmycin on animals and humans. At present, no study is available on the detection of hainanmycin in edible tissues of animals. Hence, a fast and accurate detection method for hainanmycin is essential. This study aimed to develop a new analytical method based on ultra-high-performance liquid chromatography-tandem mass spectrometry to detect hainanmycin in 10 matrices, including milk, eggs, fat, kidney, muscles and livers of chicken, beef and sheep. The limit of detection and the limit of quantitation of the 10 matrices were 0.1-0.4 µg/kg and 0.25-1 µg/kg, respectively, and were far below the maximum residue limits of other polyether anticoccidial drugs (1-150 µg/kg). The recoveries of hainanmycin ranged from 79% to 105%, and the relative standard deviation ranged from 2.8% to 12.0%. The research results prove that the proposed method is operational and simple in detecting hainanmycin, and has high precision and accuracy in a variety of matrices.

Synergistic combination of Sapindoside A and B: A novel antibiofilm agent against Cutibacterium acnes.

Sapindus saponins extracted from Sapindus mukorossi Gaertn. have been reported to exert antibacterial activity against Cutibacterium acnes (C. acnes). However, there are no reports about their potentials against its biofilm, which is a major contributor to the antibiotic resistance of C. acnes. This study aimed to investigate the synergistic antibiofilm activity and action of the combination of Sapindoside A and B (SAB) against C. acnes. SAB with sub-MICs significantly inhibited the early-formed and mature biofilm of C. acnes and decreased the adhesion and cell surface hydrophobicity (p < 0.05). Also, SAB greatly reduced the production of exopolysaccharide and lipase (p < 0.05), and the binding mode of SAB and lipase was predicted by molecular docking, via hydrogen bonds and hydrophobic interactions. Biofilm observed with electron microscopies further confirmed the high antibiofilm activity of SAB against C. acnes. Furthermore, a significant down-regulation of biofilm biosynthesis-associated genes was observed. The combination index explained the synergistic effects of SAB leading to the above results, and the contribution of SA was greater than that of SB. The current results showed that SAB had synergistic antibiofilm activity against C. acnes, and the Sapindoside A played a major role, indicating that SAB could be a natural antiacne additive against C. acnes biofilm-associated infections.

Isolation of two sesquiterpene glycosides from Sapindus mukorossi Gaertn. with cytotoxic properties and analysis of their mechanism based on network pharmacology.

The anti-tumor effects of two compounds purified from Sapindus mukorossi Gaertn. (S. mukorossi.) on breast cancer in vitro were observed. Their chemical structures were identified as sesquiterpene glycosides, namely, Mukurozioside IIa and Mukurozioside IIb. The results of XTT assay indicated that their inhibition rates against three cancer cell lines (MCF-7, MDA-MB-231 and MDA-MB-435s) reached approximately 80% at a concentration of 200 µg/mL, which were higher than that of cyclophosphamide (below 40% at 200 µg/mL), and their 50% inhibiting concentrations were ranged from 120.73 to 154.01 µg/mL, indicating their inhibition were weaker than their parent fraction. Furthermore, the mechanism on breast cancer was predicted, and 22 targets including PTPN1, IL2 and VEGFA were relatively important. These results illustrated the anti-breast cancer activity of S. mukorossi was related to the two compounds with the structure of sesquiterpene glycosides, but they did not represent the full activity of their parent fraction.

Potent in vitro synergistic antibacterial activity of natural amphiphilic Sapindoside A and B against Cutibacterium acnes with destructive effect on bacterial membrane.

Sapindus saponins are obtained from the outer bark of Sapindus mukorossi Gaertn. (S. mukorossi), and they have become an interesting subject in the search for new anti-acne agents without resistance. This study aimed to screen the synergistic antibacterial combination from Sapindus saponins and investigated the synergistic antibacterial action via targeting the cell membrane of Cutibacterium acnes (C. acnes) to reduce the effective dose. The combination of Sapindoside A and B (SAB) was obtained with synergistic activity against C. acnes. SAB led to the leakage of ions and disturbed the membrane morphology of C. acnes. The spectral features of cell membrane composition showed obvious changes based on Raman spectroscopy, and changes in membrane protein microenvironment were also observed by fluorescence spectroscopy. Among the above results, the contribution of Sapindoside A was greater than that of Sapindoside B to the synergistic combination of SAB. Furthermore, molecular docking demonstrated that Sapindoside A interacted with penicillin-binding protein 2, playing an important role in peptidoglycan synthesis for the cross wall, and showed a higher binding score than Sapindoside B, further indicating that the greater contribution in the synergistic action of SAB on membrane proteins. Collectively, these results showed that the synergistic antibacterial action of SAB against C. acnes could be achieved by attacking cell membrane, and Sapindoside A played a major role, suggesting that SAB has the potential to be the natural anti-acne agent additive in the cosmetic industry.

Synergistic antibacterial combination of Sapindoside A and B changes the fatty acid compositions and membrane properties of Cutibacterium acnes.

Sapindus saponins extracted from S. mukorossi have been reported to exert antibacterial activities against skin pathogenic bacteria, but their antibacterial mechanism is still at an exploratory stage. The objective of this study was to explore the synergistic antibacterial mechanism of the combination of two Sapindus saponins, namely Sapindoside A and B (SAB) against Cutibacterium acnes (C. acnes) 6919 via targeting the fatty acid compositions and membrane properties. After exposure to SAB, C. acnes cells increased the cell surface hydrophobicity and reduced the cell membrane fluidity by changing the composition of membrane fatty acids. In the fatty acid compositions, the content of two main fatty acids 12-methyl-tetradecanoic acid (isoC15:0) and octadecanoic acid (C18:0) reduced and improved respectively with the addition of SAB, and fatty acid biosynthesis-related genes were significantly down-regulated (p < 0.05). Further, molecular docking demonstrated that SAB interacted with FabD, which is an essential enzyme for bacterial type II fatty acid synthesis, via hydrogen bonds and hydrophobic interactions. In the above results, the contribution of SA to SAB was greater than that of SB. In summary, the results revealed that SAB changed the fatty acid compositions of C. acnes, further disrupting the cell membrane properties, and SA played a major role, suggesting that SAB could be a natural antiacne additive against C. acnes-associated infections.

The chemical profile and biological activity of different extracts of Sapindus mukorossi Gaertn. against Cutibacterium acnes.

This study evaluated the antibacterial activities of different extracts of Sapindus mukorossi Gaertn. (S. mukorossi) on Cutibacterium acnes (C. acnes). The extract solvent and procedure were screened, based on the yield of saponins and minimum inhibitory concentration (MIC). The results showed that the optimized product, fermentation and ethyl acetate extract by adding isoamyl alcohol from water extract of S. mukorossi (SWFEAI), had the highest yield of saponins (7.83 ± 0.26%) and the best antibacterial activity (MIC = 0.125 mg/mL) on C. acnes. The destroyed bacterial cell membrane and wall were observed by transmission electron microscopy, which then resulted in cell lysis and death. Furthermore, 20 compounds of SWFEAI were detected, among which oleanane-type triterpenoid saponins with molecular weights of 734, 750, 882, 924 and 966 were speculated to contribute to the antibacterial activities of SWFEAI. The results showed that SWFEAI could be a natural anti-acne agent.