Hyperoside exerts osteoprotective effect on dexamethasone-induced osteoblasts by targeting NADPH Oxidase 4 (NOX4) to inhibit the reactive oxygen species (ROS) accumulation and activate c-Jun N-terminal kinase (JNK) pathway.

Hyperoside (Hyp) is a flavonoid active compound deriving from Chinese herbal medicines. Increasing studies have implicated that Hyp may serve as a predominant promoting factor in osteoblast differentiation. This paper investigates whether Hyp could relieve glucocorticoid-induced osteonecrosis of the femoral head (GONFH) via promoting osteoblast survival and differentiation as well as to uncover its potential mechanism. GONFH cell model was induced by treating MC3T3-E1 cells with dexamethasone (DEX). The viability, apoptosis, and osteogenic differentiation of DEX-induced cells with the presence or absence of Hyp were assessed by CCK-8, Tunel, ALP assay, and ARS staining, respectively. The NADPH Oxidase 4 (NOX4) overexpression was performed by transfection with overexpression vector. Besides, western blot was used to determine the levels of apoptosis-, osteogenic differentiation-, and c-Jun N-terminal kinase (JNK) signaling-related proteins. It was noticed that Hyp caused no significant effects on the viability of MC3T3-E1 cells without any treatment but significantly enhanced the viability of DEX-induced cells. Besides, Hyp inhibited the apoptosis in DEX-induced cells but enhanced ALP activity and calcium nodule formation. Additionally, Hyp declined NOX4 expression in DEX-induced cells. However, NOX4 overexpression partially reversed the impacts of Hyp on DEX-exposed MC3T3-E1 cells. Finally, Hyp suppressed the activation of ROS/JNK pathway in DEX-induced cells, which was then counteracted by NOX4 overexpression. In conclusion, Hyp could promote the survival and differentiation of DEX-induced osteoblasts by targeting NOX4 to inhibit the ROS/JNK pathway. These results provide evidence for the application of Hyp in treating GONFH.

Ancient and modern medication laws of aromatic Chinese medicines in treating angina pectoris based on data mining / 数字中医药（英文）

@#Objective To explore ancient and modern medication laws of aromatic Chinese medicines in treating angina pectoris, and to provide new ideas for the clinical treatment. Methods With “angina pectoris” as the key word, ancient books prescriptions and Chinese patent medicines related to angina pectoris were collected from China National Knowledge Infrastructure (CNKI), Traditional Chinese Medicine Database System, Chinese Medicine Prescription Database, New National Proprietary Chinese Medicine (2nd edition), and Chinese Pharmacopoeia (2020 edition) from January 1, 2015 to December 31, 2021. Core high-frequency aromatic Chinese medicines were defined, and their potential medication rules were analyzed and summarized. Microsoft Access 2010 was used for data management. Data analysis software, including Excel and IBM SPSS Modeler 18.0 were used for drug association rule analysis, and Cytoscape 3.7.2 for visual display. Results There were 67 ancient books prescriptions and 258 Chinese patent medicines containing aromatic Chinese medicines treating angina pectoris collected from relevant databases. In ancient books prescriptions, there were nine aromatic Chinese medicines with the frequency ≥10, and the most commonly used medicine was Danggui (Angelicae Sinensis Radix), followed by Chenpi (Citri Reticulatae Pericarpium). There were 33 aromatic Chinese medicines with the frequency ≥10 in Chinese patent medicines, and the most commonly used medicine was Danshen (Salviae Miltiorrhizae Radix et Rhizoma), followed by Chuanxiong (Chuanxiong Rhizoma) and Sanqi (Notoginseng Radix et Rhizoma). In ancient books prescriptions, the medicines mainly belonged to intenal-warming medicines, Qi-regulating medicines, and blood circulation promoting and blood stasis removing medicines. There were eight medicine pairs with confidence equal to 100% in ancient books prescriptions, the most frequently used pairs were Chuanxiong (Chuanxiong Rhizoma) + Danggui (Angelicae Sinensis Radix), and Xiangfu (Cyperi Rhizoma) + Chenpi (Citri Reticulatae Pericarpium). In Chinese patent medicines, the aromatic Chinese medicine Chuanxiong (Chuanxiong Rhizoma) could be combined with many other Chinese medicines, among which the Confidence and Support of Chuanxiong (Chuanxiong Rhizoma) + Danshen (Salviae Miltiorrhizae Radix et Rhizoma) were at a high level. Conclusion Aromatic Chinese medicines for the treatment of angina pectoris of coronary heart disease are mainly warm, and the flavors are mainly pungent, sweet, and bitter. They mainly access to the liver, gallbladder, and pericardium meridians. The treatment of angina pectoris of coronary heart disease mainly focuses on warming heart pulse, and promoting blood circulation and removing blood stasis.

Pharmacokinetics of five phthalides in volatile oil of Ligusticum sinense Oliv.cv. Chaxiong, and comparison study on physicochemistry and pharmacokinetics after being formulated into solid dispersion and inclusion compound.

BACKGROUNDS: The dried rhizome of Ligusticum sinense Oliv.cv. Chaxiong has been used to treat cardiovascular and cerebrovascular diseases, atherosclerosis, anemia and stroke. A high purity extract from chaxiong (VOC, brownish yellow oil) was extracted and separated. Its main components were senkyunolide A (SA, 33.81%), N-butylphthalide (NBP, 1.38%), Neocnidilide (NOL, 16.53%), Z-ligustilide (ZL, 38.36%), and butenyl phthalide (BP, 2.48%), respectively. Little is known about the pharmacokinetics of these phthalides in Chaxiong, and different preparations to improve the physicochemistry and pharmacokinetics of VOC have not been investigated. METHODS: At different predetermined time points after oral administration or intravenous administration, the concentrations of SA, NBP, NOL, ZL and BP in the rat plasma were determined using LC-MS/MS, and the main PK parameters were investigated. VOC-P188 solid dispersion and VOC-ß-CD inclusion compound were prepared by melting solvent method and grinding method, respectively. Moreover, the physicochemical properties, dissolution and pharmacokinetics of VOC-P188 solid dispersion and VOC-ß-CD inclusion compound in rats were assessed in comparison to VOC. RESULTS: The absorptions of SA, NBP, NOL, ZL and BP in VOC were rapid after oral administration, and the absolute bioavailability was less than 25%. After the two preparations were prepared, dissolution rate was improved at pH 5.8 phosphate buffer solution. Comparing VOC and physical mixture with the solid dispersion and inclusion compound, it was observed differences occurred in the chemical composition, thermal stability, and morphology. Both VOC-P188 solid dispersion and VOC-ß-CD inclusion compound had a significantly higher AUC and longer MRT in comparison with VOC. CONCLUSION: SA, NBP, NOL, ZL and BP in VOC from chaxiong possessed poor absolute oral bioavailability. Both VOC-P188 solid dispersion and VOC-ß-CD inclusion compound could be prospective means for improving oral bioavailability of SA, NBP, NOL, ZL and BP in VOC.

A new triterpenoid and a new flavonoid glycoside isolated from Bupleurum marginatum and their anti-inflammatory activity.

This study to investigate chemical constituents from the aerial of Bupleurum marginatum led to the isolation of a new trierpenoid and a new flavonoid, namely 3ß-hydroxy-cycloart-24-en-26-acetyloxy (1), and 3, 3', 5'-trimethoxyl-myricetin 7-O-ß-D-glucopyranoside (2) along with eight known compounds (3-10). Their structures were established by spectral data analyses (MS, 1D and 2D NMR), as well as by comparison of spectral data with those of the related known compounds. The 24-en-lanostane type triterpenoid with a cyclopropane ring (1 and 3) was firstly reported from this specie, which might be chemotaxonomic markers of this specie. In addition, compounds 1 and 2 were examined for their anti-inflammatory activity. Compounds 1 and 2 inhibited the NF κB induction by 60.61% and 24.30%.