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This study was done in order to investigate the changes of the major biochemical components and in vitro antioxidant activity of the water extracts from different kinds of tea during the process of their multistage membrane separation, ultrafiltration membranes with molecular masses cut-off (MMCO) of 20, 10, and 3.5 kDa, respectively were successively used to separate the water extracts from the major kinds of tea in Fujian including green tea, white tea, oolong tea from south Fujian, oolong tea from north Fujian, and black tea into fractions with different molecular masses. The fractions were spray dried and investigated for their ultraviolet (UV) spectra, biochemical compositions and in vitro antioxidant activity. The results showed that the UV absorption spectra of all samples were similar, exhibiting two obvious peaks at 210 and 274 nm. Absorbance at 274 nm exhibited a significant positive correlation with the contents of free amino acids (FAAs), caffeine (CAF), gallic acid (GA) and epicatechin gallate (ECG), and a significantly negative correlation with the contents of epigallocatechin (EGC) and epicatechin (EC). The distribution of biochemical components and the changes in antioxidant activity in vitro were affected by membrane separation, among which, the 20 kDa MMCO membrane had the most pronounced impact. The retentate from black tea after 20 kDa MMCO membrane ultrafiltration had the highest antioxidant activity in vitro, while the antioxidant activity of the permeate was lower than that of the permeate from the other kinds of tea. The biochemical components and antioxidant activity in vitro varied significantly among different types of tea samples, and the changes in biochemical components and antioxidant activity during the membrane separation process were not completely consistent. The water extract from black tea showed the greatest changes after 20 kDa MMCO membrane ultrafiltration. These results could provide a scientific basis for the membrane separation of aqueous extracts from different types of tea.

This study introduces a novel approach for synthesizing Benzoxazine‐centered Polychiral Polyheterocycles (BPCPHCs) via an innovative asymmetric carbene‐alkyne metathesis‐triggered cascade. Overcoming challenges associated with intricate stereochemistry and multiple chiral centers, the catalytic asymmetric Carbene Alkyne Metathesis‐mediated Cascade (CAMC) is employed using dirhodium catalyst/Brønsted acid co‐catalysis, ensuring precise stereo control as validated by X‐ray crystallography. Systematic substrate scope evaluation establishes exceptional diastereo‐ and enantioselectivities, creating a unique library of BPCPHCs. Pharmacological exploration identifies twelve BPCPHCs as potent Nav ion channel blockers, notably compound 8 g. In vivo studies demonstrate that intrathecal injection of 8 g effectively reverses mechanical hyperalgesia associated with chemotherapy‐induced peripheral neuropathy (CIPN), suggesting a promising therapeutic avenue. Electrophysiological investigations unveil the inhibitory effects of 8 g on Nav1.7 currents. Molecular docking, dynamics simulations and surface plasmon resonance (SPR) assay provide insights into the stable complex formation and favorable binding free energy of 8 g with C5aR1. This research represents a significant advancement in asymmetric CAMC for BPCPHCs and unveils BPCPHC 8 g as a promising, uniquely acting pain blocker, establishing a C5aR1‐Nav1.7 connection in the context of CIPN. [ABSTRACT FROM AUTHOR]

Neuropathic pain is a refractory chronic disease affecting millions of people worldwide. Given that present painkillers have poor efficacy or severe side effects, developing novel analgesics is badly needed. The multiplex structure of active ingredients isolated from natural products provides a new source for phytochemical compound synthesis. Here, we identified a natural product, Narirutin, a flavonoid compound isolated from the Citrus unshiu, showing antinociceptive effects in rodent models of neuropathic pain. Using calcium imaging, whole-cell electrophysiology, western blotting, and immunofluorescence, we uncovered a molecular target for Narirutin's antinociceptive actions. We found that Narirutin (i) inhibits Veratridine-triggered nociceptor activities in L4-L6 rat dorsal root ganglion (DRG) neurons, (ii) blocks voltage-gated sodium (NaV) channels subtype 1.7 in both small-diameter DRG nociceptive neurons and human embryonic kidney (HEK) 293 cell line, (iii) does not affect tetrodotoxin-resistant (TTX-R) NaV channels, and (iv) blunts the upregulation of Nav1.7 in calcitonin gene-related peptide (CGRP)-labeled DRG sensory neurons after spared nerve injury (SNI) surgery. Identifying Nav1.7 as a molecular target of Narirutin may further clarify the analgesic mechanism of natural flavonoid compounds and provide an optimal idea to produce novel selective and efficient analgesic drugs. [ABSTRACT FROM AUTHOR]

This study introduces a novel approach for synthesizing Benzoxazine-centered Polychiral Polyheterocycles (BPCPHCs) via an innovative asymmetric carbene-alkyne metathesis-triggered cascade. Overcoming challenges associated with intricate stereochemistry and multiple chiral centers, the catalytic asymmetric Carbene Alkyne Metathesis-mediated Cascade (CAMC) is employed using dirhodium catalyst/Brønsted acid co-catalysis, ensuring precise stereo control as validated by X-ray crystallography. Systematic substrate scope evaluation establishes exceptional diastereo- and enantioselectivities, creating a unique library of BPCPHCs. Pharmacological exploration identifies twelve BPCPHCs as potent Nav ion channel blockers, notably compound 8 g. In vivo studies demonstrate that intrathecal injection of 8 g effectively reverses mechanical hyperalgesia associated with chemotherapy-induced peripheral neuropathy (CIPN), suggesting a promising therapeutic avenue. Electrophysiological investigations unveil the inhibitory effects of 8 g on Nav1.7 currents. Molecular docking, dynamics simulations and surface plasmon resonance (SPR) assay provide insights into the stable complex formation and favorable binding free energy of 8 g with C5aR1. This research represents a significant advancement in asymmetric CAMC for BPCPHCs and unveils BPCPHC 8 g as a promising, uniquely acting pain blocker, establishing a C5aR1-Nav1.7 connection in the context of CIPN., (© 2024 Wiley-VCH GmbH.)