An integrated strategy of spectrum-effect relationship and near-infrared spectroscopy rapid evaluation based on back propagation neural network for quality control of Paeoniae Radix Alba.

The quantitative analysis of near-infrared spectroscopy in traditional Chinese medicine has still deficiencies in the selection of the measured indexes. Then Paeoniae Radix Alba is one of the famous "Eight Flavors of Zhejiang" herbs, however, it lacks the pharmacodynamic support, and cannot reflect the quality of Paeoniae Radix Alba accurately and reasonably. In this study, the spectrum-effect relationship of the anti-inflammatory activity of Paeoniae Radix Alba was established. Then based on the obtained bioactive component groups, the genetic algorithm, back propagation neural network, was combined with near-infrared spectroscopy to establish calibration models for the content of the bioactive components of Paeoniae Radix Alba. Finally, three bioactive components, paeoniflorin, 1,2,3,4,6-O-pentagalloylglucose, and benzoyl paeoniflorin, were successfully obtained. Their near-infrared spectroscopy content models were also established separately, and the validation sets results showed the coefficient of determination (R2 > 0.85), indicating that good calibration statistics were obtained for the prediction of key pharmacodynamic components. As a result, an integrated analytical method of spectrum-effect relationship combined with near-infrared spectroscopy and deep learning algorithm was first proposed to assess and control the quality of traditional Chinese medicine, which is the future development trend for the rapid inspection of traditional Chinese medicine.

Palladium-Catalyzed Branch- and Z-Selective Allylic C-H Amination with Aromatic Amines.

Allylamines are important building blocks in the synthesis of bioactive compounds. The direct coupling of allylic C-H bonds and commonly available amines is a major synthetic challenge. An allylic C-H amination of 1,4-dienes has been accomplished by palladium catalysis. With aromatic amines, branch-selective allylic aminations are favored to generate thermodynamically unstable Z-allylamines. In addition, more basic aliphatic cyclic amines can also engage in the reaction, but linear dienyl allylic amines are the major products.

Single Standard Substance for the Simultaneous Determination of Eleven Components in the Extract of Paeoniae Radix Alba (Root of Paeonia lactiflora Pall.).

Paeoniae Radix Alba (PRA), an herbal drug produced from the root of Paeonia lactiflora Pall., is widely used in many herbal medicine prescriptions/preparations. Since the pharmacological effects of PRA come from multiple chemical components, it is important to establish a method for the determination of those components in PRA extracts with simple operation and low cost, which is more suitable to evaluate the quality of PRA extracts and optimize the extraction process. This work introduced the quantitative analysis of multicomponents with a single-marker (QAMS) method for the simultaneous determination of eleven bioactive components in PRA extracts, including gallic acid, oxypaeoniflorin, catechin, albiflorin, paeoniflorin, ethyl gallate, galloylpaeoniflorin, pentagalloylglucose, benzoic acid, benzoylpaeoniflorin, and paeonol. In the QAMS method established based on high performance liquid chromatography with diode array detection, only the reference substance of paeoniflorin was needed, and the other ten components were determined based on their relative correction factors (RCFs) to paeoniflorin. Moreover, the repeatability and robustness of the RCFs were studied with different column temperatures, detection wavelengths, flow rates, column types, and instruments. In method validation, good linearity (r > 0.999), stability, repeatability (RSD < 1.9%), and accuracy (recoveries within 96.1%-105.5%) were shown. Sample analyses showed that the QAMS method was consistent with the conventional external standard method. The established method provided a comprehensive, efficient, and low-cost tool for the routine quality evaluation of PRA extracts.

Kangtaizhi Granule Alleviated Nonalcoholic Fatty Liver Disease in High-Fat Diet-Fed Rats and HepG2 Cells via AMPK/mTOR Signaling Pathway.

Kangtaizhi granule (KTZG) is a Chinese medicine compound prescription and has been proven to be effective in nonalcoholic fatty liver disease (NAFLD) treatment clinically. However, the underlying mechanisms under this efficacy are rather elusive. In the present study, network pharmacology and HPLC analysis were performed to identify the chemicals of KTZG and related target pathways for NAFLD treatment. Network pharmacology screened 42 compounds and 79 related targets related to NAFLD; HPLC analysis also confirmed six compounds in KTZG. Further experiments were also performed. In an in vivo study, SD rats were randomly divided into five groups: control (rats fed with normal diet), NAFLD (rats fed with high-fat diet), and KTZG 0.75, 1.5, and 3 groups (NAFLD rats treated with KTZG 0.75, 1.5, and 3 g/kg, respectively). Serum lipids were biochemically determined; hepatic steatosis and lipid accumulation were evaluated with HE and oil red O staining. In an in vitro study, HepG2 cells were incubated with 1 mM FFA to induce lipid accumulation with or without KTZG treatment. MTT assay, intracellular TG level, oil red O staining, and glucose uptake in cells were detected. Western blotting and immunohistochemical and immunofluorescence staining were also performed to determine the expression of lipid-related genes PPAR-γ, SREBP-1, p-AKT, FAS, and SIRT1 and genes in the AMPK/mTOR signaling pathway. In high-fat diet-fed rats, KTZG treatment significantly improved liver organ index and serum lipid contents of TG, TC, LDL-C, HDL-C, ALT, and AST significantly; HE and oil red O staining also showed that KTZG alleviated hepatic steatosis and liver lipid accumulation. In FFA-treated HepG2 cells, KTZG treatment decreased the intracellular TG levels, lipid accumulation, and attenuated glucose uptake significantly. More importantly, lipid-related genes PPAR-γ, SREBP-1, p-AKT, FAS, and SIRT1 expressions were ameliorated with KTZG treatment in high-fat diet-fed rats and FFA-induced HepG2 cells. The p-AMPK and p-mTOR expressions in the AMPK/mTOR signaling pathway were also modified with KTZG treatment in high-fat diet-fed rats and HepG2 cells. These results indicated that KTZG effectively ameliorated lipid accumulation and hepatic steatosis to prevent NAFLD in high-fat diet-fed rats and FFA-induced HepG2 cells, and this effect was associated with the AMPK/mTOR signaling pathway. Our results suggested that KTZG might be a potential therapeutic agent for the prevention of NAFLD.

Merging Visible-Light Photoredox and Chiral Phosphate Catalysis for Asymmetric Friedel-Crafts Reaction with in Situ Generation of N-Acyl Imines.

In the presence of visible-light photoredox and chiral phosphate catalysts, a novel asymmetric Friedel-Crafts reaction of indoles and readily accessible α-amino acid derived redox-active esters is established to afford enantioenriched 1-indolyl-1-alkylamine derivatives in moderate to high yields and with high levels of enantioselectivities. This method not only shows a mild and efficient alternative for the in situ generation of N-acyl imines but also indicates the feasibility of a multicatalyst system for asymmetric photoredox catalysis.

Advancement in the chemical analysis of Paeoniae Radix (Shaoyao).

Paeoniae Radix Alba (baishao or white peony root) and Paeoniae Radix Rubra (chishao or red peony root) are two highly valuable traditional Chinese medicines (TCMs) usually indicated for painful conditions, menstrual disorders and viral infections. These two TCMs are collectively referred to as shaoyao (Paeoniae Radix) due to their close origins and similar chemical compositions. Modern research indicates that monoterpene glycosides, polyphenols and paeonols are the three main types of compounds related to the pharmacological activities of Paeoniae Radix. This review summarizes recent advances in the chemical analysis of Paeoniae Radix and the related traditional Chinese medicine formulas/preparations, including methods used for sample pretreatment, qualitative analysis, quantitative analysis and biological sample analysis. More than 120 papers are discussed in this review, focusing on the chemical analysis of Paeoniae Radix, and various analytical techniques (such as HPLC, LC-MS, IR, near IR and quantitative NMR), as well as their advantages/disadvantages, are described. It is our hope that this paper can provide necessary information for improving the quality evaluation methods currently available for Paeoniae Radix and offer a scientific basis for the future in-depth study of the pharmacokinetics and pharmacodynamics of Paeoniae Radix.

Access to Chiral Hydropyrimidines through Palladium-Catalyzed Asymmetric Allylic C-H Amination.

A palladium-catalyzed asymmetric intramolecular allylic C-H amination controlled by a chiral phosphoramidite ligand was established for the preparation of various substituted chiral hydropyrimidinones, the precursors of hydropyrimidines, in high yields with high enantioselectivities. In particular, dienyl sodium N-sulfonyl amides bearing an arylethene-1-sulfonyl group underwent a sequential allylic C-H amination and intramolecular Diels-Alder (IMDA) reaction to produce chiral fused tricyclic tetrahydropyrimidinone frameworks in high yields and with high levels of stereoselectivity. Significantly, this method was used as the key step in an asymmetric synthesis of letermovir.