Potential targets and mechanism of Houpuwenzhongtang for the treatment of spleen and stomach deficiency cold stomach disease based on network pharmacology / 中国药理学通报

Aim To explore the potential targets and mechanisms of Houpuwenzhongtang for the treatment of spleen and stomach deficiency cold stomach disease. Methods Firstly, TCMSP database, disease database and compound target prediction platform were used to collect active components, disease targets and predict potential targets. Secondly, Cytoscape 3.7.2 and String platform were used to screen key chemical components and core targets, and PPI network diagram was constructed. Finally, The active components with degree greater than 30 were used for molecular docking with key targets, and some docking results were selected for cell experiment. Results The key active components of Houpuwenzhongtang in the treatment of spleen and stomach deficiency cold stomach disease were hesperidin, magnolol, 6-gingerol, and so on. The key targets were JUN, AKT1, IL-8, etc.. The related pathways mainly involved immune response, signaling transduction, cell proliferation and apoptosis. Molecular docking results showed that the key active components had good binding activity with disease targets. The results of cell experiments showed that magnolol, hesperidin and 6-gingerol had different degrees of anti-inflammatory activity against IL-8 in a dose-dependent manner. Conclusions It is speculated that Houpuwenzhongtang may act on IL-8, JUN, AKT1 and other targets through magnolol, hesperidin,6-gingerol and other active ingredients, and participate in the regulation of PI3K-AKT signaling pathway, N F-K B signaling pathway for the treatment of spleen and stomach deficiency cold stomach disease. And it is found for the first time that 6-gingerol could stably bind to multiple disease targets related spleen and stomach deficiency cold stomach disease,such as AKT1,IL-8 and so on. The result suggests that 6-gingerol is worth further research. Through the results of IL-8 cell experiment, it is speculated that the components such as magnolol and hesperidin may play a role in gastric diseases caused by Helicobacter pylori infection by reducing the content of IL-8 in gastric mucosa.

Comparative Analysis of Effect of Houpu Wenzhongtang Combined Decoction and Simple Decoction on Urine Metabonomics of Rats with Deficiency-cold of Spleen and Stomach / 中国实验方剂学杂志

Objective:To study the effect of combined decoction and single decoction of Houpu Wenzhongtang on rats with deficiency-cold of spleen and stomach from the perspective of metabonomics, to find out the relevant potential biomarkers and metabolic pathways, and to explore the similarities and differences between the combined decoction and single decoction, so as to provide reference for the feasibility analysis of replacing traditional decoction with single dispensing granule of this formula. Method:SD rats were randomly divided into normal group, model group, Houpu Wenzhongtang combined decoction group and simgle decoction group. Rats in the normal group were given distilled water by intragastric administration, rats in the other three groups were given cold vinegar at 4 ℃ in the morning and refined lard in the afternoon for 10 days (the dosage of 10 mL·kg-1). After the model was successfully established, rats in the combined decoction group and the single decoction group were given corresponding decoction with dosage of 1.8 g·kg-1 (according to the amount of crude drugs), once a day for 7 days. Ultra-high liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS) technique was used to analyze the small molecular endogenous metabolites in urine. Orthogonal partial least squares-discriminant analysis (OPLS-DA) and principal component analysis (PCA) were used to compare the changes of differential metabolites among the normal group, model group, Houpu Wenzhongtang combined decoction group and single decoction group, and the differential metabolites were introduced into Kyoto Encyclopedia of Genes and Genomes (KEGG) for metabolic pathway analysis. Result:Compared with the model group, the Houpu Wenzhongtang combined decoction group and single decoction group jointly regulated 13 potential biomarkers, including phosphatidylcholine(PC), lysophosphatidic acid(LysoPA) and cholic acid, etc. They played a role in treating deficiency-cold of spleen and stomach by influencing metabolic pathways such as glycerophospholipid metabolism, glycerolipid metabolism, phosphatidylinositol signaling system and so on. The combined decoction and single decoction of Houpu Wenzhongtang could obviously restore the body weight, motilin and gastrin contents of rats with deficiency-cold of spleen and stomach to normal levels. Conclusion:According to biochemical indexes, there is no obvious difference between combined decoction and single decoction of Houpu Wenzhongtang, but according to metabonomics, the combined decoction may be slightly better than the single decoction. The research shows that it is feasible to replace traditional decoction with single dispensing granule of Houpu Wenzhongtang in clinical application.

Research Progress of Houpo Wenzhongtang / 中国实验方剂学杂志

Houpo Wenzhongtang was contained in Neiwaishang bianhuolun.It was composed of seven medicinal materials of Magnoliae Officinalis Cortex(processed with ginger),Citri Reticulatae Pericarpium(remove white sac),Glycyrrhizea Radix et Rhizoma(processed with honey),Alpiniae Katsumadai Semen,Poria,Aucklandiae Radix and Zingiberis Rhizoma.It was a classic prescription for treatment of deficient cold of spleen and stomach,distention of chest and abdomen,autumn and winter guest cold crime stomach and feel pain at times by LI Dongyuan,who was a famous doctors in Jin-Yuan dynasties.It has been included in the Catalogue of Ancient Classical Prescription(The First Batch) issued by the State Administration of Traditional Chinese Medicine in 2018.This paper systematically reviewed the relevant research progress of Houpo Wenzhongtang from the aspects of famous doctors' theory,usage and dosage,chemical composition,quality analysis,pharmacology and toxicology,clinical application in database,and to provide a reference for further exerting the clinical application of this classical prescription.

Phenolic Components from Roots of Psidium guajava / 中国实验方剂学杂志

Objective:The different parts of Psidium guajava(Myrrhinaceae) have different bioactivities. There are intensive studies for chemical constituents of its leaves and fruits at present. However,there are a few studies for the roots. Therefore, we systematically investigated the chemical constituents of phenolic acids in roots of P.guajava. Method:The chemical constituents were isolated and purified by various column chromatography methods and semi-preparative HPLC. The isolated compounds were identified by physicochemical properties and spectral analysis. Result:Sixteen phenolic components were isolated from the ethanol extract and identified as 3,3',4'-tri-O-methylellagic acid(1),3,3',4-tri-O-methylellagic acid-4'-O-β-D-glucopyranoside(2),3-O-methylellagic acid-4'-O-α-L-rhamnopyranoside(3),3'-O-methyl-3,4-O,O-metheneellagic acid-4'-O-β-D-glucopyranoside(4),gallic acid(5),methyl gallate(6),ethyl gallate(7), 3,4,5-trimethoxypheny-1-β-D-glucopyranoside(8),3,5-dimethoxy-4-hydroxy-benzoic acid-7-O-β-D-glucoside(9),1-hydroxy-3,4,5-trimethoxyphenyl-1-O-[6'-O-(4″-carboxy-1″,3″,5″-trihydroxy)phenyl]-β-D-glucopyranoside(10),vanillic acid(11),protocatechuic acid(12),secoisolariciresinol 9-O-β-D-glucopyranoside(13),phloretin 4'-O-β-D-glucopyranoside(14),cinchonain Ib(15) and epicatechin(16). Conclusion:Compounds 3,4,6,8-10,13-15 were isolated from this plant for the first time.

A new triterpenoid from roots of Psidium guajava / 药学学报

To investigated the chemical constituents of the roots of Psidium guajava,we isolated seven compounds by silica gel column chromatography.These include oleanane derivatives,2 α,3β,6β,23-tetrahydroxylurs-12,20(30)-dien-28-oic acid β-D-glucopyranoside (1),2α,3β,6β,23-tetrahydroxylurs-12,18-dien-28-oic acid β-D-glucopyranoside (2),2α,3β,23-trihydroxylurs-12,18-dien-28-oic acid β-D-glucopyranoside (3), nigaichigoside F1(4),asiaticoside C (5),2α,3β,6β,19α,23-pentahydroxylurs-12,18-dien-28-oic acid β-Dglucopyranoside (6) and 2α,3β,19α,23-tetrahydroxylurs-12-en-28-oic acid (7).Their structures were elucidated on the basis of spectral analysis with reference to the published data.Compound 1 is brand new,compounds 2-6 were first isolated from this plant.The new compound was evaluated for their cytotoxic activity against human hepatoma Bel 7402 in vitro.The results were expressed as the ratio of inhibiting Bel 7402 cells growth by comparing to untreated cells.The new compound (concentration:25 μmol·L-1) showed the ratio values of 52.5%.

UPLC/ESI-QTOF-MS-based metabolomics survey on the toxicity of triptolide and detoxication of licorice / 中国天然药物

Triptolide (TP) from Tripterygium wilfordii has been demonstrated to possess anti-inflammatory, immunosuppressive, and anticancer activities. TP is specially used for the treatment of awkward rheumatoid arthritis, but its clinical application is confined by intense side effects. It is reported that licorice can obviously reduce the toxicity of TP, but the detailed mechanisms involved have not been comprehensively investigated. The current study aimed to explore metabolomics characteristics of the toxic reaction induced by TP and the intervention effect of licorice water extraction (LWE) against such toxicity. Obtained urine samples from control, TP and TP + LWE treated rats were analyzed by UPLC/ESI-QTOF-MS. The metabolic profiles of the control and the TP group were well differentiated by the principal component analysis and orthogonal partial least squares-discriminant analysis. The toxicity of TP was demonstrated to be evolving along with the exposure time of TP. Eight potential biomarkers related to TP toxicity were successfully identified in urine samples. Furthermore, LWE treatment could attenuate the change in six of the eight identified biomarkers. Functional pathway analysis revealed that the alterations in these metabolites were associated with tryptophan, pantothenic acid, and porphyrin metabolism. Therefore, it was concluded that LWE demonstrated interventional effects on TP toxicity through regulation of tryptophan, pantothenic acid, and porphyrin metabolism pathways, which provided novel insights into the possible mechanisms of TP toxicity as well as the potential therapeutic effects of LWE against such toxicity.

Flavonoids from leaves of Psidum littorale / 药学学报

We investigated the chemical constituents of the leaves of Psidum littorale, which include 16 flavonoids, including seven flavonols, six flavonoid glycosides and three flavonones. The compounds were isolated by silica gel column chromatography. Their structures were elucidated on the basis of spectral analysis and by comparison with published data. Seven flavonols were kaempferol (1), isorhamnetin (2), myricetin-3,7,3'-trimethyl ether (3), laricitrin (4), quercetin (5), myricetin (6) and quercein-3,4'-dimethyl ether (7), six flavonoid glycosides were guaijaverin (8), hyperoside (9), 5,4'-dyhydroxy-3,7,5'-methoxyflavone-3'-O-β-D-glucoside (10), laricitrin-3-O-xyloside (11), myricetin-3-O-α-L-rhamnopyranoside (12) and myricetin-3-O-β-D-xyloside (13). Three flavonones were 4'-O-methyldihydroquercetin (14), dihydroapigenin (15) and ampelopsin 4'-O-β-D-glucopyranoside (16). Compound 10 is a new chemical, compounds 2-4, 7, 10-16 were first isolated from this plant. 1H NMR and 13C NMR data of compound 11 were not reported in literature.

Quality standard study on Pteris multifida / 中国中药杂志

The quality control method and standard were established to control the quality of Pteris multifida in this paper. The tests of water content, total ash, acid-unsoluble ash and ethanol-soluble extractives of P. multifida were carried out according to the methods recorded in appendix of Chinese Pharmacopeia (2010 edition, volume 1) . The TLC method was established by using rhoifolin as references, and a mixture of CHCl3 -MeOH-HAc (6: 1: 1) as the developing solvent system on GF254 thin layer plate. The contents of rhoifolin was determined by HPLC on a Diamonsil C18 (4.6 mm x 250 mm, 5 μm) column, using acetonitrile-water (containing 0.15% formic acid) (16: 84) as mobile phase at a flow rate of 1.0 mL x min(-1). The column temperature was 30 degrees C and the detection wave-length was 350 nm. As a result, pterosin C 3-O-β-D-glucosidede and the other constituents were well separated on TLC detected under the UV light at 254 nm . The methodology validation for the assay of rhoifolin presented that it was in good linear correlation in the ranges of 0.025 5-5.1 μg with the regression equations of Y = 1 092.4X + 9.503 5 (r = 0.999 8), and the average recoveries were 100.3% (RSD 1.3%). The content range of rhoifolin from 16 different batches of Pteris multifida was 0.08-5.06 mg x g(-1). The water content, total ash, acid-unsoluble ash and ethanol-soluble extractives of 16 samples varied in the ranges of 7.35% - 12.96%, 6.90% - 16.33%, 2.07% -11.38% and 13.29% -23.87%, respectively. The suggesting limes in the quality standard for water content, total ash, acid-unsoluble ash, ethanol-soluble extractives and rhoifolin content were ≤ 12% , ≤ 15% , ≤ 8.5% , ≥ 14% and ≥ 0.040%, respectively. The result proved that the established quality of control method was specific and accurate, which can be used for the quality control of P. multifida.

Terpenoid compounds isolated from Ligularia sagitta / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents of radix and rhizome of Ligularia sagitta.</p><p><b>METHOD</b>Isolation and purification were carried out on the column chromatography of silica gel and sephadex LH -20. The structures were identified by spectral analysis.</p><p><b>RESULT</b>Seven terpenoid compounds were isolated from the radix and rhizome of L. sagitta. Five of them are sesquiterpenoids, the structures were determined as 7alpha-hydroxy-9(10) -ene-1, 8-dioxo-6, 7-dihydrofuranoeremophilane (1), 1p, 10P3-epoxy-6beta, 8 beta-dihydroxy-eremophil7 (11) -en-12, 8alpha-olide (2) , 1-oxo-9-desoxycacalol (3), benzofuranoeremophil-l-ene (4) and bakkenolide (5); other two compounds belong to triterpenoid. 3p, 16P3-dihydroxy-12-oleanen-28-al (6) and lupeol (7).</p><p><b>CONCLUSION</b>Compoundsl-3 and 6 were: isolated from L. sagitta for the first time, and compounds 3 and 6 were obtained from Ligularia for the first time.</p>