Ginsenosides are the main active ingredients in ginseng and have recently been reported to have beneficial effects on the CNS. Ocotillol is a derivate of pseudoginsenoside-F11, which is an ocotillol-type ginsenoside found in American ginseng. We examined the effects of ocotillol (a) on neuronal activity of projection neurons, mitral cells (MC), in a mouse olfactory bulb brain slice preparation using whole-cell patch-clamp recording, and (b) on animal behavior by measuring locomotor activity of mice in vivo. Ocotillol displayed an excitatory effect on spontaneous action potential firing and depolarized the membrane potential of MCs. The effect was concentration-dependent, with an EC(50) of 4 μM. In the presence of blockers of ionotropic glutamatergic and GABAergic synaptic transmission (6-cyano-7-nitroquinoxaline-2,3-dione [CNQX], 10 μM; D-AP5, 50 μM; gabazine, 5 μM), the excitatory effect of ocotillol on firing was abolished. Further experiments showed that the ocotillol-induced neuronal excitation persisted in the presence of GABA(A) receptor antagonist gabazine but was eliminated by applying AMPA/kainate receptor antagonist CNQX and N-methyl-d-aspartate (NMDA) receptor antagonist D-AP5, suggesting that ionotropic glutamate transmission was involved in mediating the effects of ocotillol. Bath application of ocotillol evoked an inward current as well as an increased frequency of spontaneous glutamatergic excitatory postsynaptic currents (EPSCs). Both the inward current and sEPSCs could be blocked by ionotropic glutamate receptor antagonists CNQX and D-AP5. These results indicate that the excitatory action of ocotillol on MCs was mediated by enhanced glutamate release. Behavioral experiments demonstrated that ocotillol increased locomotor activities of mice. Our results suggest that ocotillol-evoked neuronal excitability was mediated by increased release of glutamate, which may be responsible for the increased spontaneous locomotor activities in vivo.

Ginseng derivative ocotillol enhances neuronal activity through increased glutamate release: a possible mechanism underlying increased spontaneous locomotor activity of mice

Dammarane-type leads panaxadiol and protopanaxadiol for drug discovery: Biological activity and structural modification

20(S)-Protopanaxadiol (PPD) is a basic aglycone of the dammarane triterpenoid saponins and exerts antidepressant-like effects on behaviour in the forced swimming test (FST) and tail suspension test (TST) and in rat olfactory bulbectomy depression models. However, the antidepressant effects of PPD have not been studied thoroughly. The objective of the present study was first to investigate the effect of PPD on depression behaviours induced by chronic social defeat stress (CSDS) in mice. The results showed that CSDS was effective in producing depression-like behaviours in mice, as indicated by decreased responses in the social interaction test, sucrose preference test, TST, and FST, and that this effect was accompanied by noticeable alterations in the levels of oxidative markers (superoxide dismutase, catalase, and lipid peroxidation) and monoamines (5-HT and NE) in the hippocampus and serum corticosterone levels. Additionally, western blot analysis revealed that CSDS exposure significantly downregulated BDNF, p-TrkB/TrkB, p-Akt/Akt, and p-mTOR/mTOR protein expression in the hippocampus. Remarkably, chronic PPD treatment significantly ameliorated these behavioral and biochemical alterations associated withCSDS-induced depression. Our results suggest that PPD exerts antidepressant-like effects in mice with CSDS-induced depression and that this effect may be mediated by the normalization of neurotransmitter and corticosterone levels and the alleviation of oxidative stress, as well as the enhancement of the PI3K/Akt/mTOR-mediated BDNF/TrkB pathway.

Antidepressant-like effects of 20(S)-protopanaxadiol in a mouse model of chronic social defeat stress and the related mechanisms

Zeaxanthin and lutein have a wide range of pharmacological applications. In this study, we conducted systematic experimental research to optimize antioxidant extraction based on detection, extraction, process amplification, and purification. An ultrasonic-assisted method was used to extract zeaxanthin and lutein with high efficiency from corn gluten meal. Firstly, the effects of solid-liquid ratio, extraction temperature, and ultrasonic extraction time on the extraction of zeaxanthin were investigated in single-factor experiments. The optimization extraction parameters of zeaxanthin and lutein with ethanol solvent were obtained using the response surface methodology (RSM) as follows: liquid-solid ratio of 7.9:1, extraction temperature of 56 °C, and extraction time of 45 min. The total content of zeaxanthin and lutein was 0.501%. The optimum extraction experimental parameters were verified by process amplification, and we confirmed that the parameters of the extraction process optimized using the RSM design are reliable and precise. Zeaxanthin and lutein from crude extract of corn gluten were separated and purified using silica gel column chromatography with the purity of zeaxanthin increasing from 0.28% to 31.5% (about 110 times) and lutein from 0.25% to 16.3% (about 65 times), which could be used for large-scale industrial production of carotenoids.

https://www.mdpi.com/1420-3049/24/16/2994/pdf

Optimization of Ultrasonic-Assisted Extraction and Purification of Zeaxanthin and Lutein in Corn Gluten Meal

Antibiotic resistance mediated by bacterial enzymes constitutes an unmet clinical challenge for public health, particularly for those currently used antibiotics that are recognized as “last-resort” defense against multidrug-resistant (MDR) bacteria. Inhibitors of resistance enzymes offer an alternative strategy to counter this threat. The combination of inhibitors and antibiotics could effectively prolong the lifespan of clinically relevant antibiotics and minimize the impact and emergence of resistance. In this review, we first provide a brief overview of antibiotic resistance mechanism by bacterial secreted enzymes. Furthermore, we summarize the potential inhibitors that sabotage these resistance pathways and restore the bactericidal activity of inactive antibiotics. Finally, the faced challenges and an outlook for the development of more effective and safer resistance enzyme inhibitors are discussed.

/pdf/molecules-that-inhibit-bacterial-resistance-enzymes-4lrc8d37nr.pdf

Molecules that Inhibit Bacterial Resistance Enzymes.

Ginseng is a perennial herb that contains various medicinal substances. The major active constituents of ginseng are ginsenosides, which have multifarious biological activities. Some pharmacological activities are closely dependent on the stereoisomers derived from the configuration at C20. In this study, the in vitro anti-inflammatory activity of C20 epimeric ocotillol-type triterpenes (2, 3, 9: , and 10: ) and protopanaxadiol [20(S/R)-protopanaxadiol] were investigated. Epimers 2: and 3: were prepared starting from 20(S)-protopanaxadiol. Epimers 9: and 10: were synthesized from 20(R)-3-acetylprotopanaxadiol (7: ). The anti-inflammatory activity of 2, 3, 9, 10: , 20(S)-protopanaxadiol, and 20(R)-protopanaxadiol was evaluated in cultured mouse macrophage RAW 264.7 cells. The MTT assay was used to measure the cytotoxicity. RAW 264.7 cells were stimulated by lipopolysaccharide to release the inflammatory mediators nitric oxide, prostaglandin E2, TNF-α, and interleukin-6 and anti-inflammatory mediator interleukin-10. The effect of the compounds on the overproduction of nitric oxide, prostaglandin E2, TNF-α, interleukin-6, and interleukin-10 was determined using Griess and ELISA methods. The results demonstrated that the in vitro anti-inflammatory activities of C20 epimeric ocotillol-type triterpenes and protopanaxadiol were different. Both the 20S-epimers (2: and 3: ) and 20R-epimers (9: and 10: ) inhibited the release of inflammatory mediator nitric oxide, while mainly the 20S-epimers inhibited the release of inflammatory mediator prostaglandin E2, and the 20R-epimers inhibited the release of inflammatory cytokine TNF-α. Both the 20S-epimers [2, 3: , and 20(S)-protopanaxadiol] and 20R-epimers [9, 10: , and 20(R)-protopanaxadiol] inhibited the release of inflammatory cytokine interleukin-6, but mainly the 20S-epimers [2, 3: , and 20(S)-protopanaxadiol] increased the release of anti-inflammatory mediator interleukin-10.

Synthesis and In Vitro Anti-inflammatory Activity of C20 Epimeric Ocotillol-Type Triterpenes and Protopanaxadiol.

Phytochemistry, bioactivities and future prospects of mulberry leaves: A review.

Oleanolic acid can inhibit edema and exhibit obvious inhibitory activity to inflammatory by activating of the pituitary-adrenal cortical system, inhibiting the synthesis or release of PGs, inhibiting endotoxin-mediated release of HMGB1 by endothelial cells or regulating MAPK, PI3K/Akt/NF- κB/ICAM-1/JAK/STAT signaling pathways, etc In recent years, an increased number of interesting research work has been carried out on the anti-inflammatory activity and mechanisms of OA derivatives, such as acyloxyimino derivative, 3-acetylated derivatives, novel 3,5-disubstituted isoxazoles derivatives, acetate, ester derivatives and oximes derivatives The review summaries and highlights the updated advances on the anti-inflammatory activity and mechanism of OA and its derivatives

Advances on the Anti-inflammatory Activity of Oleanolic Acid and Derivatives.

Abstract C19H14F4O2${\\text{C}}_{19}{\\text{H}}_{14}{\\text{F}}_{4}{\\text{O}}_{2}$, triclinic, P1‾$P‾{1}$ (no. 2), a = 8.1539(7) Å, b = 8.8584(6) Å, c = 11.8025(9) Å, α = 73.186(7)°, β = 76.184(7)°, γ = 69.512(7)°, V = 755.39(11) Å3, Z = 2, Rgt${R}_{gt}$(F) = 0.0436, wRref$w{R}_{\\text{ref}}$(F2) = 0.0965, T = 100 K.

/pdf/crystal-structure-of-e-2-4-fluoro-3-trifluoromethyl-1e0u1bra7f.pdf

Crystal structure of (E)-2-(4-fluoro-3-(trifluoromethyl)benzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2H)-one, C19H14F4O2

Abstract C19H14F4O2, monoclinic, C2/c (no. 15), a = 17.1519(13) Å, b = 13.9810(8) Å, c = 15.2299(9) Å, β = 123.031(7)°, V = 3061.9(4) Å3, Z = 8, Rgt(F) = 0.0410, wRref(F2) = 0.1010, T = 100(1) K.

/pdf/crystal-structure-of-e-2-4-fluoro-2-trifluoromethyl-3rdtloowsi.pdf

Feng-Lan Zhao

Papers

Synthesis and In Vitro Anti-inflammatory Activity of C20 Epimeric Ocotillol-Type Triterpenes and Protopanaxadiol.

Phytochemistry, bioactivities and future prospects of mulberry leaves: A review.

Advances on the Anti-inflammatory Activity of Oleanolic Acid and Derivatives.

Crystal structure of (E)-2-(4-fluoro-3-(trifluoromethyl)benzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2H)-one, C19H14F4O2

Crystal structure of (E)-2-(4-fluoro-2-(trifluoromethyl)benzylidene)-7-methoxy-3,4-dihydronaphthalen-1(2H)-one, C19H14F4O2