Three novel dalbergiphenol hybrids from the heartwood of Dalbergia cochinchinensis.

A novel discovery of two hybrid benzodioxepin-dalbergiphenol epimers, named cochindalbergiphenols A-B (1-2), and a benzofuran-dalbergiphenol hybrid, named cochindalbergiphenol C (3), were isolated and identified from the heartwood of Dalbergia cochinchinensis. The structures of all the isolated compounds were identified through NMR and HRESIMS techniques, while the absolute configurations were determined by comparing the experimental and calculated ECD spectra. Compounds 1-3 exhibited potential protective effects against hypoxia/reoxygenation (H/R) induced injury in H9c2 cells.

Metabolomics of the anti-inflammatory effect of Pueraria lobata and Pueraria lobata var. Thomsonii in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Pueraria lobata (Willd.) Ohwi and Pueraria lobata var. Thomsonii (Benth.) Maesen are essential medicinal and edible homologous plants widely cultivated in Asian countries. Therefore, P. lobata and P. thomsonii are widely used in the food, health products and pharmaceutical industries and have significant domestic and international market potential and research value. P. lobata and P. thomsonii have pharmacological effects in the clinic, such as antipyretic, analgesic, anti-inflammatory and antioxidant effects. These plants are commonly used in the treatment of inflammatory diseases and other related diseases. However, the potential mechanisms of the anti-inflammatory effects of P. lobata and P. thomsonii have not been elucidated. AIM OF THE STUDY: This study aimed to confirm the anti-inflammatory effects of P. lobata and P. thomsonii on inflammatory model diseases and to investigate the mechanism of their anti-inflammatory effects from the perspective of plasma metabolomics. MATERIALS AND METHODS: First, P. lobata and P. thomsonii were identified by high‒performance liquid chromatography (HPLC). Second, we established the following three inflammation models: an acute inflammation model of auricular swelling in mice induced by xylene, an acute inflammation model of foot swelling in rats induced by carrageenan gum, and a chronic inflammation model of cotton ball granuloma in rats. Then we examined the weight and swelling rate of auricular swelling in mice; the residence time, contact area, and mean contact pressure in rats on the gait meter; and the weight of granulomas in rats and the content of IL-1ß and TNF-α in plasma to investigate the anti-inflammatory pharmacodynamics of P. lobata and P. thomsonii. Third, we used LC‒MS‒based plasma metabolomics techniques to obtain potential biomarkers of P. lobata and P. thomsonii related to inflammation. Then, the potential biomarkers were enriched by MetaboAnalyst and KEGG metabolomics analysis tools to obtain metabolic pathways related to inflammation. Finally, we tested the indicators of COX-2, 5-LOX, GSH, GSSG and γ⁃GCL in rat plasma from the granuloma model by enzyme-linked immunosorbent assays (ELISAs) to verify the inflammation-related metabolic pathway. RESULTS: The experimental results showed that P. lobata and P. thomsonii could reduce the swollen weight and swelling rate of the auricle in mice, and could increase the residence time, contact area and mean contact pressure in rats on the gait meter. Moreover, P. lobata and P. thomsonii could inhibit the growth of granulomas and reduce the content of IL-1ß and TNF-α in plasma in rats. The above results preliminarily verified that P. lobata and P. thomsonii have different anti-inflammatory effects. We identified eighteen plasma biomarkers associated with P. lobata and sixteen plasma biomarkers related to P. thomsonii in regulating inflammation by a plasma metabolomics analysis. The following two major metabolic pathways were further screened and enriched: arachidonic acid metabolism and glutathione metabolism. Then we noted that P. lobata and P. thomsonii could reduce the COX-2, 5-LOX and GSSG levels and increase the GSH, GSH/GSSG and γ⁃GCL levels based on the ELISA results, which demonstrated that P. lobata and P. thomsonii affect the anti-inflammatory mechanism through arachidonic acid metabolism and glutathione metabolism. CONCLUSIONS: The results of this study further elucidate the anti-inflammatory mechanism of action of P. lobata and P. thomsonii, providing a scientific basis for developing new drugs for the treatment of inflammation-related diseases and laying a foundation for the development of herbal resources, such as P. lobata and P. thomsonii.

[Quality evaluation of Dalbergiae Odoriferae Lignum by HPLC fingerprint and multi-component quantitative analysis].

The present study detected the component content in Dalbergiae Odoriferae Lignum by HPLC fingerprint and the multi-component determination method. HPLC analysis was performed on the Agilent ZORBAX SB-C_(18) column(4.6 mm×250 mm, 5 µm). Acetonitrile-0.5% phosphoric acid aqueous solution with gradient elution was employed as the mobile phase. The flow rate was 1.0 mL·min~(-1) and the column temperature was maintained at 30 ℃. The detection wavelength was 210 nm and the sample volume was 10 µL. The similarity of 18 batches of Dalbergiae Odoriferae Lignum was 0.343-0.779, indicating that there were great differences between different batches of Dalbergiae Odoriferae Lignum. Eighteen common peaks were identified, including eight flavonoids such as liquiritigenin and latifolin. The mass fractions of liquiritigenin, luteolin, naringenin, isoliquiritigenin, formononetin, dalbergin, latifolin, and pinocembrin were in the ranges of 0.134 1%-0.495 2%, 0.028 2%-0.167 0%, 0.016 3%-0.591 3%, 0.053 5%-0.188 0%, 0.142 4%-0.640 1%, 0.068 0%-0.590 7%, 0.003 2%-1.980 7%, and 0.009 6%-0.740 2%, respectively. Eighteen batches of Dalbergiae Odoriferae Lignum were divided into three categories by cluster analysis and eight differential components in Dalbergiae Odoriferae Lignum were marked by partial least-squares discriminant analysis(PLS-DA). The cumulative variance contribution rate was 90.5%. The HPLC fingerprint combined with the multi-component determination method for Dalbergiae Odoriferae Lignum is easy in operation and accurate in results, with good repeatability and reliability. The quality of Dalbergiae Odoriferae Lignum can be evaluated and analyzed by the PLS-DA model. This study is expected to provide a reference for the quality control and clinical application of Dalbergiae Odoriferae Lignum.

[Comparative study of rat serum pharmacochemistry between Puerariae Lobatae Radix and Puerariae Thomsonii Radix based on UPLC-Q-TOF-MS].

UPLC-Q-TOF-MS and serum pharmacochemistry were employed to study the migrating components in rat sera after intragastric administration of the water extracts of Puerariae Lobatae Radix(PLR) and Puerariae Thomsonii Radix(PTR). After the respective intragastric administration of PLR and PTR extracts, blood samples were collected from the orbital vein. The serum samples were treated by protein precipitation method with methanol and acetonitrile at a ratio of 1∶1 and then passed through Agilent ZORBAX RRHD SB-C_(18) column(3 mm×100 mm, 1.8 µm) and Agilent SB-C_(18) pre-column(3 mm×5 mm, 1.8 µm) with 0.1% formic acid aqueous solution(A)-acetonitrile(B) as the mobile phase. The elution was performed at the flow rate of 0.25 mL·min~(-1), the column temperature of 40 ℃, and the injection volume of 2 µL. By comparison of the total ion chromatogram and secondary fragment ion information of PLR and PTR water extracts, PLR-and PTR-containing sera, and blank serum, we found 42 migrating components(including 17 prototype components and 25 metabolites) in the sera of rats treated with PLR and 35 migrating components(including 15 prototype components and 20 metabolites) in the sera of rats treated with PTR. Thirty-three common components were shared by the two treatments, including 13 prototype components and 20 metabolites. The differences of migrating components in the PLR-and PTR-treated rat sera provide a scientific basis for further study of the active components and quality markers of PLR and PTR.

An image-based fingerprint-efficacy screening strategy for uncovering active compounds with interactive effects in Yindan Xinnaotong soft capsule.

BACKGROUND: Yindan Xinnaotong soft capsule (YDXNT) is a clinically effective herbal prescription used for the treatment of cardiovascular and cerebrovascular diseases. Since Chinese medicines (CMs) exert their effects via a "multiple-components and multiple-targets" mode, discovery of the active compounds with interactive effects may contribute to reveal their mechanisms of action. PURPOSE: This study aimed to establish an image-based fingerprint-efficacy screening strategy to identify active compounds with interaction effects from CM prescription, using YDXNT to inhibit microglia-mediated neuroinflammation as an instance. METHODS: A multi-component random content-oriented chemical library of YDXNT was constructed by uniform design, and their chemical fingerprint was profiled by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) methods. Then the neuroinflammation activities of chemical library members of YDXNT were determined by image-based dual phenotypic quantification. Subsequently, fingerprint-efficacy correlation and random forest analysis were applied to predict the potentially active compounds with interactive effects. Finally, the interactive effects among the active compounds were confirmed by quantitative polymerase chain reaction (qPCR) and apoptosis analysis, and network pharmacology was applied to explore the possible mechanisms. RESULTS: Image-based fingerprint-efficacy correlation analysis revealed that six tanshinones (TNs) and four flavonoids (FAs) were potential anti-neuroinflammatory compounds. The inter-family of TNs and FAs possessed obvious interactive effects (combination index ≤ 0.825). Moreover, the combination of scutellarein and tanshinone I (2:1, w/w) was discovered as the possible interactive combinatorial components, which, comparing with individual scutellarein or tanshinone I, shown more powerful effects on anti-inflammatory and anti-apoptotic effects in lipopolysaccharide (LPS)-induced BV2 cells. Network pharmacology showed that the active compounds might suppress microglia-mediated neuroinflammation via multiple targets in the T cell receptor, Jak-STAT, and Toll-like receptor signaling pathways. CONCLUSION: The image-based fingerprint-efficacy strategy simplifies the screening process of efficacious component combinations in CMs for complex diseases, which also offers a promising approach to explore the integrative therapeutic mechanisms of CMs.

[Research advances in chemical constituents and pharmacological activities of Pueraria genus].

Kudzu plants in the subfamily sphenoideae of Leguminosae are commonly used herbs in China, Japan, Korea, India and Thailand, with a long history of medicinal use. They are recorded in Chinese Pharmacopoeia, Japanese Pharmacopeia, Korea Pharmacopeia, Ayurveda Pharmacopoeia of India and Flora of Thailand. There are 15-20 species of Pueraria in the world, including 7 species and 2 varieties in China. At present, there are 6 species with medicinal value, such as Pueraria lobata and P. thomsonii. The main chemical components of the genus are isoflavones, flavonoids, terpenes, steroids, coumarins, puerarin glycosides and benzopyrans. A total of 240 compounds have been isolated and identified from this genus, and their pharmacological effects mainly include improvement of the cardiovascular system, antioxidant, hypoglycemic, antipyretic, anti-inflammatory, anti-alcoholic and estrogen-like effects. In this study, chemical constituents and pharmacological activities of Pueraria at home and abroad were systematically summarized, in order to provide references for the material basis, quality control and further development of Pueraria genus.

Advanced Studies on Rhizoma Dioscoreae Collettii.

Rhizoma Dioscoreae Collettii, is known as Huang Dioscorea collettii, Rhizoma Coptidis Brevisepalae or yellow ginger. It is neutral in nature and bitter in taste which is described to Gan (Liver) meridian, Wei (Stomach) meridian and Pangguang (Bladder) meridian. It was often used in the treatment of chyloid stranguria, gonorrhea, leucorrhagia, rheumatism arthralgia pain, joints disable, and lumbar knee pain syndrome in clinical.

[Study on neoflavonoids from heartwood of Dalbergia latifolia].

Dalbergiae Odoriferae Lignum is derived from heartwood of Dalbergia odorifera,which is national Ⅱ level of rare and endangered protective plants in China. Its resources are scarce and its price is high. In order to find substitutes of D. odorifera,the chemical constituents of 70% ethanol extract of heartwood of D. catifolia were systematically studied by using silica gel,Sephadex LH-20 column chromatography,and semi-preparative HPLC. Sixteen neoflavanoids were isolated and identified as eight dalbergiphenols( 1-8),three dalbergiones( 9-11),two dalbergins( 12,13),two benzophenones( 14,15) and one other type neoflavanoids( 16) based on spectroscopic data analyses and/or comparing the spectroscopic data with those in literature. Among them,compounds 3,7 and 11 were isolated from the genus Dalbergia for the first time,and compounds 2,4-6,8,14 and 15 were isolated from the D. latifolia for the first time. Ten neoflavonoids were both discovered from D. latifolia and D. odorifera.