Protective effect of Qingluotongbi formula against Tripterygium wilfordii induced liver injury in mice by improving fatty acid ß-oxidation and mitochondrial biosynthesis.

CONTEXT: Qingluotongbi formula (QLT) is a Chinese medicine compound consisting of Tripterygium wilfordii Hook. f. (Celastraceae, TW), Panax notoginseng (Burkill) F.H.Chen (Araliaceae, PN), Rehmannia glutinosa (Gaertn.) DC. (Orobanchaceae, RG), Sinomenium acutum (Thunb.) Rehder & E.H. Wilson (Menispermaceae, SA), and Bombyx mori L. (Bombycidae, BM). OBJECTIVE: This study investigated the protective effect and possible mechanism of QLT against TW-induced liver injury in mice. MATERIALS AND METHODS: To establish the model of TW-induced liver injury in mice, C57BL/6J mice were randomly divided into 4 groups: control group, low-dose TW group, middle-dose TW group, and high-dose TW group. To observe the effects of QLT and its individual ingredients against TW-induced liver injury, C57BL/6J mice were randomly divided into 7 groups: control group, TW group, QLT group, PN group, RG group, SA group, BM group.After administration for 7 days, C57BL/6J mice were tested for biochemical indicators and liver pathological changes. Then, we evaluated the mitochondrial function and analysed the gene and protein expression related to the peroxisome proliferator-activated receptor alpha (PPARα)/peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) pathway by quantitative real-time PCR (qRT-PCR) and Western blotting. RESULTS: Compared with the control group (0.30 ± 0.35), TW significantly increased mice liver histological score (L, 0.95 ± 1.14; M, 1.25 ± 1.16; H, 4.00 ± 1.13). QLT and its ingredients significantly improved the pathology scores (CON, 0.63 ± 0.74; TW, 4.19 ± 1.53; QLT, 1.56 ± 0.62; PN, 1.94 ± 0.68; RG, 2.75 ± 1.39; SA, 4.13 ± 0.99; BM, 4.13 ± 0.99). Western blot and qRT-PCR analysis revealed that QLT and its ingredients reversed TW-induced suppression of PPARα/PGC1-α pathway.Discussion and conclusions: These findings provide valuable information for compound compatibility studies and TW clinical applications.

Regulatory Effect of Quyu Huatan Tongmai Prescription on Intestinal Microflora in Golden Hamster with Hyperlipidemia / 中国实验方剂学杂志

ObjectiveTo explore the regulatory effect of Quyu Huatan Tongmai prescription on intestinal mircoflora of hyperlipidemia golden hamster and scientific evidence for the compatibility. MethodSyrian golden hamsters were randomized into normal， model， prescription， stasis-dispelling （Quyu）， phlegm-dissolving （Huatan）， and detoxification （Jiedu） groups， with 8 in each group. Hyperlipidemia in golden hamsters was induced by high-fat diet （4 weeks）. Then hamsters in the Quyu group （1.11 g·kg-1）， Huatan group （0.39 g·kg-1）， Jiedu group （0.07 g·kg-1）， and prescription group （1.42 g·kg-1） were given （ig） corresponding drugs and those in the normal group and the model group received （ig） distilled water of equivalent volume， once a day for 6 weeks. Serum lipids were determined， and hematoxylin-eosin （HE） staining was used to observe the pathological morphology of the liver. Feces were collected for 16S rRNA gene high-throughput sequencing of intestinal flora. ResultCompared with normal group， the model group demonstrated increase in body weight （P<0.05， P<0.01） and blood lipids （P<0.01）， decrease in intestinal flora diversity （P<0.05， P<0.01）， and variation of the relative abundance of intestinal flora at phylum， family， and genus levels （P<0.05， P<0.01）. Compared with the model group， Quyu Huatan Tongmai prescription controlled the body weight change， reduced the serum triglyceride （TG）， total cholesterol （TC）， and low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio （LDL-C/HDL-C） （P<0.05， P<0.01）， improved the structure of intestinal flora， decreased the ratio of Firmicutes to Bacteroides （P<0.01）， raised the abundance of Bacteroidaceae， Porphyromonadaceae， Rikenellaceae， and Pasteurella （P<0.05， P<0.01）， and lowered the relative abundance of Coriobacterium （P<0.05） in hyperlipidemia golden hamsters. All the split prescriptions improved blood lipids and intestinal flora of the hamsters and particularly， the lipids-lowering effect of the Jiedu group and the regulation of flora in the Huatan group were closer to those of the prescription group. ConclusionQuyu Huatan Tongmai prescription and the split prescriptions all alleviated the hyperlipidemia of golden hamsters to different degrees possibly by regulating intestinal flora structure and improving intestinal microecology. The effect of the prescription group was most significant， and coming in second was the Huatan group. This study also provides scientific evidence for the effect of Quyu Huatan Tongmai prescription.

[Study on compatibility of active ingredients of Simiao Yongan Decoction in rats with in situ single-pass intestinal perfusion model].

To study the compatibility rule of Simao Yongan Decoction,the rat single pass intestinal perfusion model in situ was used in this study. On the basis of early research,the five kinds of anti-inflammatory active ingredients,i.e. chlorogenic acid,liquiritin,hyperoside,angoroside C and isochlorogenic acid C in Simao Yongan Decoction were selected as research objects. The contents of the above five actives compounds with various compatibility combinations and in different intestinal segment perfusates were determined by using the method of ultra-performance liquid chromatography-mass spectrometry( UPLC-MSn). The kinetic parameters of intestinal absorption of the five anti-inflammatory active ingredients were calculated,which could be used to evaluate the intestinal absorption of each component in different combinations. The results showed that the absorption parameters of liquiritin in ileum were highest in Glycyrrhizae Radix et Rhizoma single herb,while the absorption parameters of other four components in ileum and duodenum were highest in the compatible combinations. Among them,the absorption parameters of chlorogenic acid in ileum and duodenum were highest in the whole prescription compatibility; ischlorogenic acid C showed higher absorption levels in the whole prescription and the herb compatibility of Lonicerae Japonicae Flos-Scrophulariae Radix-Glycyrrhizae Radix et Rhizoma. However,the absorption levels of hyperoside and angoroside C in different compatibilities were quite different in ileum and duodenum. In this study,the intestinal absorption of five anti-inflammatory active ingredients in Simiao Yongan Decoction with different compatibility combinations was investigated,revealing that the absorption of active ingredients varied with the different compatibility combinations and different intestinal segments. At the same time,the above research also indicated that the absorption of active ingredients could be obviously promoted by the compatibility of compound prescriptions,laying a foundation for the research on the compatibility rule of Simiao Yongan Detection from the biological point of view.

Study on compatibility of active ingredients of Simiao Yongan Decoction in rats with in situ single-pass intestinal perfusion model / 中国中药杂志

To study the compatibility rule of Simao Yongan Decoction,the rat single pass intestinal perfusion model in situ was used in this study. On the basis of early research,the five kinds of anti-inflammatory active ingredients,i.e. chlorogenic acid,liquiritin,hyperoside,angoroside C and isochlorogenic acid C in Simao Yongan Decoction were selected as research objects. The contents of the above five actives compounds with various compatibility combinations and in different intestinal segment perfusates were determined by using the method of ultra-performance liquid chromatography-mass spectrometry( UPLC-MSn). The kinetic parameters of intestinal absorption of the five anti-inflammatory active ingredients were calculated,which could be used to evaluate the intestinal absorption of each component in different combinations. The results showed that the absorption parameters of liquiritin in ileum were highest in Glycyrrhizae Radix et Rhizoma single herb,while the absorption parameters of other four components in ileum and duodenum were highest in the compatible combinations. Among them,the absorption parameters of chlorogenic acid in ileum and duodenum were highest in the whole prescription compatibility; ischlorogenic acid C showed higher absorption levels in the whole prescription and the herb compatibility of Lonicerae Japonicae Flos-Scrophulariae Radix-Glycyrrhizae Radix et Rhizoma. However,the absorption levels of hyperoside and angoroside C in different compatibilities were quite different in ileum and duodenum. In this study,the intestinal absorption of five anti-inflammatory active ingredients in Simiao Yongan Decoction with different compatibility combinations was investigated,revealing that the absorption of active ingredients varied with the different compatibility combinations and different intestinal segments. At the same time,the above research also indicated that the absorption of active ingredients could be obviously promoted by the compatibility of compound prescriptions,laying a foundation for the research on the compatibility rule of Simiao Yongan Detection from the biological point of view.

Compound Compatibility Law of Rhubarb and Aconite Decoction Based on CYP450 Enzymes / 中国药学杂志

OBJECTIVE: To study the law of compatibility and detoxification of rhubarb and aconite decoction based on the CYP450 enzyme-mediated metabolic interaction. METHODS: The activities of CYP1A2 and CYP3A4 enzymes were determined by incubating the "Cocktail" probe drugs in vitro. The total content of CYP450 enzyme in liver microsomes was determined by carbon monoxide differential method. And the expression of CYP1A2 and CYP3A4 mRNA was detected by RT-PCR method. RESULTS: Rhubarb group, aconite root combined with rhubarb group and rhubarb combined with asarum group showed significant induction effects on CYP1A2 enzyme activity. CYP1A2 enzyme activity was significantly inhibited in the aconite root combined with asarum group. CYP3A4 enzyme activity was significantly inhibited in the asarum group and the aconite root combined with asarum group. Rhubarb group, rhubarb combined with asarum group and rhubarb and aconite decoction had significant induction effects on CYP3A4 enzyme activity. Rhubarb group significantly induced the total content of CYP450 enzyme, asarum group and aconitum root combined with asarum group inhibited the total content of CYP450 enzyme, rhubarb and aconite decoction had slight induction effects on the total content of CYP450, but there was no significant difference. Rhubarb group, rhubarb combined with asarum group and rhubarb and aconite decoction group could up-regulate the mRNA expression of CYP1A2. In addition, rhubarb and aconite decoction and rhubarb group could up-regulate the mRNA expression of CYP3A4. And asarum group and aconite combined with asarum group could down-regulate the mRNA expression of CYP3A4. CONCLUSION: The drug combination weakened the strong induction of CYP1A2 and CYP3A4 enzymes by rhubarb alone, reflecting the holism concept of compound traditional Chinese medicine. The effects of rhubarb and aconite decoction on CYP3A4 enzyme activity are likely to be regulated by the mRNA levels of CYP3A4 enzyme. Whether there is correlation between the cold-heat compatibility based on the pharmacological theory and the induction or inhibition of CYP450 enzyme needs further study.

Characterization of co-amorphous complex with piperine and triterpenoids from Ligustri Lucidi Fructus and dissolution evaluation in vitro / 中草药

Objective To prepare a co-amorphous complex of piperine (PIP) and triterpenoids from Ligustri Lucidi Fructus (TLLF) to improve the dissolution of TLLF. Methods TLLF-PIP co-amorphous complex was prepared using solvent evaporation method. The microscopic structure of co-amorphous complex (CAC) was analyzed using differential scanning calorimetry (DSC), scanning electronmicroscopy (SEM), and powder X-ray diffraction (PXRD), the optimal ratio of the two components was investigated through the thermal stability experiment. Ultraviolet-visible spectrophotometry (UV-Vis) and high performance liquid chromatography (HPLC) were applied to determine the amount of TLLF, PIP and the individual components, ursolic acid (UA) and oleanolic acid (OA), respectively. The interaction of the optimal CAC was analyzed by Fourier transform infrared spectroscopy (FTIR), and its solubility and dissolution behavior in vitro were also studied to evaluate the formation of the preparation. Results PXRD analysis indicated that the TLLF-PIP-CAC with a mass ratio of 1:1 exhibited a stable amorphous state, which particles presented in near-spherical shape. FTIR results indicated that there are some hydrogen interactions between the moleculars of TLLF and PIP. The solubility and dissolution determination exhibited a pairwise released behavior with improved triterpenoids and decreased piperine dissolution. Conclusion The prepared TLLF-PIP-CAC can significantly improve the dissolution and amorphous stability of TLLF, which may provide a reference for the compatibility of insoluble compound in traditional Chinese medicine.

Herb-herb interaction in traditional Chinese medicine:a review of pharmacokinetics-based interaction in Herb-Pairs / 中国药理学与毒理学杂志

″Herb-Pairs″, also known as pair drugs, refers to a prescription consisted of two relatively fixed traditional Chinese medicine, is the most basic, most simple and most common form of medication prescription in traditional Chinese medicine compound compatibility. It is not a random combination of two herbs, nor is the simple accumulation of efficacy, but the simple and delicate experience of ancient Chinese medicine practitioners. As a bridge between single drug and prescriptions, it is the embodiment of the regular and dialectical connotation. Therefore, research on Herb-Pairs has always been the most basic and most important entry point for compound compatibility studies. However, the interaction between herbs and herbs is an effect with a downside as well as benefits. The beneficial herb-herb interaction in Herb-Pairs include mutual promotion, mutual enhancement, mutual restraint between two drugs and counteract toxicity of another drug. And the harmful herb- herb interaction in Herb- Pairs includes mutual inhibition and antagonism. All of these interactions areby means of affecting the metabolism of components to play a therapeutic effect. Using the pharmacokinetic-pharmacodynamic (PK-PD) binding model, the combination of drug metabolism and pharmacodynamics can further elucidate the influence on effect caused by drug concentration and metabolism, which can help elucidate the mechanism of drug action. Consequently, in this review, the herb-herb interactions in terms of pharmacokinetic were summarized to elucidate rule of TCM compatibility.