Acyl-quinic acids from the root bark of Acanthopanax gracilistylus and their inhibitory effects on neutrophil elastase and cyclooxygenase-2 in vitro.

Eleven new acyl-quinic acids (AQAs) 1a-9, and 18 known AQAs 10-27 were isolated from the root bark of Acanthopanax gracilistylus W. W. Smith (Acanthopanacis Cortex). The planar structures of 1a-9 were determined based on their HR-ESIMS, IR, and NMR data. The absolute configurations of 1a-6 were identified by comparing the experimental and the calculated electronic circular dichroism (ECD) spectra. This is the first report of the isolation of AQAs from Acanthopanacis Cortex. Notably, 1a-6 were determined as unusual oxyneolignan-(-)-quinic acids heterodimers, representing a new class of natural products. The inhibitory activities of 1a-27 on neutrophil elastase (NE) and cyclooxygenase-2 (COX-2) were studied in vitro, and the results indicated they possessed significant inhibitory activities on COX-2. Among them, the IC50 values of 1a-9 were 0.63±0.014, 0.75±0.028, 0.15±0.023, 0.63±0.016, 0.30±0.013, 35.63±4.600, 8.70±1.241, 16.51±0.480, 0.69±0.049, 0.39±0.017, and 0.26±0.080 µM, respectively. This study represents the inaugural disclosure of the anti-COX-2 constituents found in Acanthopanacis Cortex, thereby furnishing valuable insights into the exploration of novel COX-2 inhibitors derived from natural reservoirs.

Efficacy and mechanism of action of Yanxiao Di'naer formula for non-alcoholic steatohepatitis treatment based on metabolomics and RNA sequencing.

ETHNOPHARMACOLOGICAL RELEVANCE: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is a crucial component of this disease spectrum. The Yanxiao Di'naer formula (YXDNE) is an Uyghur medical extract that has been used in folk medicine to treat hepatitis for a long time. However, the role and mechanism of action of YXDNE in NASH treatment remains unclear. OBJECTIVE: The objective of this study was to assess the effectiveness of YXDNE in treating NASH induced by injections of carbon tetrachloride combined with a high-fat high-cholesterol diet (HFHCD), and to clarify the underlying mechanisms. METHODS: The compounds in the YXDNE extract were analysed for classification and proportions using ultra-performance liquid chromatography-mass spectrometry. The efficacy of YXDNE in treating abnormal lipid metabolism was evaluated in L02 cells in vitro. In addition, a C57BL/6 mouse model of NASH was established to evaluate the therapeutic efficacy of YXDNE in vivo. Metabolomics and RNA sequencing were used to analyse the therapeutic effects of YXDNE on the liver. The corresponding signalling pathways were found to target AMPKα1, PPARα, and NF-κB. The efficacy of YXDNE was validated using inhibitors or silencing RNA (siRNA) against AMPKα1 and PPARα. RESULTS: This study confirmed that YXDNE treatment ameliorated NASH in a murine model of this disease. Metabolomics analysis suggested that YXDNE efficacy was associated with fatty acid catabolism and AMPK signalling pathways. RNA sequencing results showed that YXDNE efficacy in treating NASH was highly correlated with the AMPK, PPARα and NF-κB pathways. Both in vitro and in vivo experimental data demonstrated that YXDNE affected the expression of p-AMPKα1, PPARα, p-NF-κB, IκB, and p-IκB. The efficacy of YXDNE in treating NASH in vitro was cancelled when AMPK was inhibited with Compound C or PPARα was modulated via siRNA. CONCLUSIONS: YXDNE may have a therapeutic effect on abnormal lipid metabolism in L02 cells and in a murine model of NASH by affecting the AMPKα1/PPARα/NF-κB signalling pathway. Therefore, YXDNE has the potential for clinical application in the prevention and treatment of NASH.

Lignan and Phthalide Derivatives from the Rhizome of Ligusticum chuanxiong (Rhizoma chuanxiong) and Evaluation of Their anti-Xanthine Oxidase Activities.

The previous research results showed that the extracts of ethyl acetate of the rhizome of Ligusticum chuanxiong (Rhizoma chuanxiong) possessed significant antigout effects in model mice. To explore the active ingredients responsible for the effects, phytochemical studies were performed, which led to the isolation of three rare 8', 9-linked neolignans, ligusticumins A-C (1-3), together with two novel phthalide-phenylpropanoid heterodimers, ligusticumalides A-B (4 and 5). It is noteworthy that 4 possesses an unprecedented 7-styryl phthalide skeleton. The structures and absolute configurations of 1-5 were elucidated by one-dimensional (1D) and two-dimensional (2D) NMR spectroscopy and electron-capture detector (ECD) spectroscopic methods. The bioassay results showed that compounds 1, 2, 3, and 5 presented moderate inhibitory activities against xanthine oxidase (XO) and 4 possessed a significant XO inhibitory effect with an IC50 value of 93.88 µM. This is the first time to investigate the anti-XO active ingredients of R. chuanxiong, which provides valuable information for searching for new antigout agents from natural products.

Monoterpenoids from the root bark of Acanthopanax gracilistylus and their inhibitory effects on neutrophil elastase, 5-lipoxygenase, andcyclooxygenase-2 in vitro.

Twenty-four monoterpenoids, including three previously undescribed compounds (1-3), were isolated from the root bark of Acanthopanax gracilistylus W. W. Smith (Acanthopanacis Cortex). Their structures were unambiguously established based on spectroscopic analysis (HR-ESIMS, IR, 1D, and 2D NMR), and the absolute configurations of 1-3 were elucidated by comparing their experimental and calculated electronic circular dichroism spectra. In addition, the structure of 8 was confirmed by single-crystal X-ray diffraction. The inhibitory activities of 1-24 against neutrophil elastase, 5-lipoxygenase, and cyclooxygenase-2 (COX-2) were studied in vitro for the first time, and the results showed that compound 24 possessed a significant inhibitory effect on COX-2 with an IC50 value of 1.53 ± 0.10 µΜ. This research first reported the presence of monoterpenoids in Acanthopanacis Cortex, including one monoterpenoid 2 with an unusual 4/5 bicyclic lactone system, and compounds 4 and 5 have never been reported in nature.

Evaluation of antioxidant, enzyme inhibition, nitric oxide production inhibitory activities and chemical profiles of the active extracts from the medicinal and edible plant: Althaea officinalis.

To develop the medicinal and edible plant resources of Althaea officinalis Linn in Europe and other places, this study concentrated on the bioactive ingredients of its different extracts. The phytochemical compositions of MeOH extracts were evaluated by UPLC-DAD-ESI-Q-TOF-MSn analysis. The in vitro antioxidant properties, enzymes inhibitory effects and nitric oxide (NO) production inhibitory activities of fractions obtained from the aerial parts of Althaea officinalis (APAO) were evaluated. The results identified 76 compounds, including 8 phenolic acids, 17 flavonoids, 6 coumarins, 9 triterpenes and 11 alkaloids. Fr. C-2 of APAO was found to have the highest TPC (175.8 ± 1.5 mg GAE/g) and TFC (466.9 ± 5.0 mg RE/g) with the highest antioxidant capacity in DPPH, ABTS, CUPRAC, FRAP and ß-carotene bleaching assays. Fr. A showed noticeable inhibition of α-glucosidase with an IC50 value of 3.8 ± 0.1 µg/mL. However, Fr. B displayed stronger inhibitory activity on 5-lipoxygenase than quercetin, with the IC50 value of 8.4 ± 1.6 µg/mL. In addition, Fr. B also possessed potent inhibitory activities on NO production toward LPS-activated RAW 264.7 Cells with an IC50 value of 15.7 ± 1.6 µg/mL. Our findings suggest that different Althaea officinalis extracts may be considered sources of phenolic and flavonoid compounds with high potential as natural antioxidants, anti-inflammatory agents and blood sugar regulators. In addition, they can also be used in food and nutraceutical products with enhanced bioactivities.