A Network Pharmacology Approach to Explore the Mechanism of HuangZhi YiShen Capsule for Treatment of Diabetic Kidney Disease.

BACKGROUND AND OBJECTIVE: HuangZhi YiShen Capsule (HZYS) is a Chinese patent herbal drug that protects kidney function in diabetic kidney disease (DKD) patients. However, the pharmacologic mechanisms of HZYS remain unclear. This study would use network pharmacology to explore the pharmacologic mechanisms of HZYS. METHODS: Chemical constituents of HZYS were obtained through the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and literature search. Potential targets of HZYS were identified by using the TCMSP and the SwissTarget Prediction databases. DKD-related target genes were collected by using the Online Mendelian Inheritance in Man, Therapeutic Target Database, GeneCards, DisGeNET, and Drugbank databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to further explore the mechanisms of HZYS in treating DKD. Molecular docking was conducted to verify the potential interactions between the prime compounds and the hub genes. RESULTS: 179 active compounds and 620 target genes were obtained, and 571 common targets were considered potential therapeutic targets. The top 10 main active compounds of HZYS were heparin, quercetin, kaempferol, luteolin, methyl14-methylpentadecanoate, methyl (Z)-11-hexadecenoate, 17-hydroxycorticosterone, 4-pregnene-17α, 20ß, 21-triol-3, 11-dione, wogonin, and hydroxyecdysone. Hub signaling pathways by which HZYS treating DKD were PI3K-Akt, MAPK, AGE-RAGE in diabetic complications, TNF, and apoptosis. The top 10 target genes associated with these pathways were IL6, MAPK1, AKT1, RELA, BCL2, JUN, MAPK3, MAP2K1, CASP3, and TNF. Quercetin and Luteolin were verified to have good binding capability with the hub potential targets IL6, MAPK1, AKT1 through molecular docking. CONCLUSION: HZYS appeared to treat DKD by regulating the inflammatory, oxidative stress, apoptotic, and fibrosis signaling pathways. This study provided a novel perspective for further research of HZYS.

Waggle needling wields preferable neuroprotective and anti-spastic effects on post-stroke spasticity rats by attenuating γ-aminobutyric acid transaminase and enhancing γ-aminobutyric acid.

Waggle needling, a classical anti-spastic needling technique characterized by combination of acupuncture with joint movement, has gained increasing popularity of spasticity treatment in China. This study was designed to compare the anti-spastic effect of waggle needling to the routine needling and to explore its underlying mechanism. We established post-stroke spasticity model based on ischemia stroke operation (middle cerebral artery occlusion). Rats were divided into six groups: normal control group, sham-operated control group, ischemia stroke model group, waggle needling group, routine needling group and baclofen group. Neurological function and muscle tone were assessed by the Zea Longa score and modified Ashworth scale, respectively. Indirect muscle tone was testified with electrophysiological recording. Cerebral infarction was measured by 2,3,5-triphenyltetrazolium chloride staining. The concentrations and expressions of γ-aminobutyric acid transaminase (GABAT) and γ-aminobutyric acid (GABA) were detected by enzyme-linked immunosorbent assay and western blot assay. Waggle needling markedly alleviated neurological deficits, decreased cerebral infarction and eased muscle tone; simultaneously, attenuated GABAT and enhanced GABA expression in the cortical infarct regions in comparison with the routine needling (P < 0.01), yet showed similar therapeutic effect to the baclofen group (P > 0.05). These results preliminary supported that waggle needling as a potential promising non-pharmacological intervention for the treatment of cerebral ischemia and spasticity.

New neo-lignan from Acanthopanax senticosus with protein tyrosine phosphatase 1B inhibitory activity.

New neo-lignan, (7S, 8R)-3-hydroxyl-4-methoxyl-balanophonin (1), together with seven known compounds (2-8) were isolated from the EtOAc-soluble extract of Acanthopanax senticosus. The structure of the new neo-lignan was elucidated with spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against PTP1B, VHR and PP1. Among them, the new compound (1) was found to exhibit selective inhibitory activity on PTP1B with IC50 value 15.2 ± 1.4 µM.

Four new sesqui-lignans isolated from Acanthopanax senticosus and their diacylglycerol acyltransferase (DGAT) inhibitory activity.

Four new sesqui-lignans, (7R, 7'R, 7″S, 8S, 8'S, 8″S)-4',5″-dihydroxy-3,5,3',4″-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol (1), (7R, 7'R, 7″S, 8S, 8'S, 8″S)-4',3″-dihydroxy-3,5,3',5',4″-pentamethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol (2), (7R, 7'R, 7″S, 8S, 8'S, 8″S)-3',4″-dihydroxy-3,5,4',5″-tetramethoxy-7,9':7',9-diepoxy-4,8″-oxy-8,8'-sesquineo-lignan-7″,9″-diol (3) and acanthopanax A (7) together with three known compounds (4-6) were isolated from the EtOAc-soluble extract of Acanthopanax senticosus. Their structures were elucidated on the basis of spectroscopic and physicochemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1 and DGAT2. Among them, compounds 1-6 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 61.1 ± 1.3 to 97.7 ± 1.1 µM and compound 7 showed selective inhibition of DGAT2 with IC50 value 93.2 ± 1.2.

Effects of Morus root bark extract and active constituents on blood lipids in hyperlipidemia rats.

OBJECTIVE: Chinese crude drug Mori Cortex Radicis (the root cortex of Morus species) has been used as a folk medicine to treat hypertension, diabetes, as well as in expectorant, diuretic agents. This investigation aims to study the anti-hyperlipidemia effects of Mori Cortex Radicis (MCR) extracts in hyperlipidemic rat models and the potential therapeutic activities of compounds isolated from the extracts. MATERIALS AND METHODS: The effects of MCR on hypolipidemic parameters were investigated using Wistar rats induced by high-lipid emulsion. Sixty healthy Wistar rats were randomly divided into 6 groups: normal group, hyperlipidaemia model group, simvastatin, and high-, medium- and low-dose MCR extracts. After four weeks, body weight, total cholesterol (TC), triglycerides (TG), high and low-density lipoproteins (HDL, LDL), as well as aspartate aminotransferase (AST), alanine aminotransferase (ALT) were measured. To further investigation, four major active compounds were isolated from extracts through high performance liquid chromatography (HPLC) and their diacylglycerol acyltransferase 1 (DGAT1) inhibitory activity was evaluated. RESULTS: MCR dose-dependently reduced serum TC, TG, LDL-C, inhibited the activity of ALT, AST, and increased HDL-C. Furthermore, in vitro biochemistry tests revealed that four active isolates showed moderate inhibitory activity against DGAT1 with IC50 values ranging from 62.1 ± 1.2 to 99.3 ± 2.3 µM. CONCLUSIONS: The results demonstrated that MCR could effectively ameliorate hyperlipidaemia and inhibit DGAT1 that a key enzyme closely related to hyperlipidaemia and type 2 diabetes. It may provide a new pharmacological basis for treating hyperlipidaemia and related diseases using MCR.

Inhibition of diacylglycerol acyltransferase by prenylated flavonoids isolated from the stem bark of Maackia amurensis.

A new prenylated flavanone, erythraddison Z (1), together with eight known flavonoids (2-9), was isolated from the stem bark of Maackia amurensis. Their structures were elucidated on the basis of spectroscopic methods, including 1D and 2D NMR (COSY, HMQC, and HMBC) techniques. All the isolates, with the exception of 3, 6 and 7, strongly inhibited diacylglycerol acyltransferase activity in an in vitro assay with IC50 values ranging from 96.5 ± 0.6 to 135.1 ± 1.4 µM.