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1.
Chin J Nat Med ; 19(12): 944-953, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34961592

ABSTRACT

Huosu Yangwei (HSYW) Formula is a traditioanl Chinese herbal medicine that has been extensively used to treat chronic atrophic gastritis, precancerous lesions of gastric cancer and advanced gastric cancer. However, the effective compounds of HSYW and its related anti-tumor mechanisms are not completely understood. In the current study, 160 ingredients of HSYW were identified and 64 effective compounds were screened by the ADMET evaluation. Furthermore, 64 effective compounds and 2579 potential targets were mapped based on public databases. Animal experiments demonstrated that HSYW significantly inhibited tumor growth in vivo. Transcriptional profiles revealed that 81 mRNAs were differentially expressed in HSYW-treated N87-bearing Balb/c mice. Network pharmacology and PPI network showed that 12 core genes acted as potential markers to evaluate the curative effects of HSYW. Bioinformatics and qRT-PCR results suggested that HSYW might regulate the mRNA expression of DNAJB4, CALD, AKR1C1, CST1, CASP1, PREX1, SOCS3 and PRDM1 against tumor growth in N87-bearing Balb/c mice.


Subject(s)
Drugs, Chinese Herbal , Stomach Neoplasms , Animals , Biomarkers , China , Mice , Network Pharmacology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics
2.
J Sci Food Agric ; 101(4): 1419-1427, 2021 Mar 15.
Article in English | MEDLINE | ID: mdl-32833246

ABSTRACT

BACKGROUND: Perilla seed oil (PSO) is the main constituent of perilla seeds currently being used in the food industry, however it also has great clinical potential in the regulation of lung function as a nutrition supplement because of the high content of α-linolenic acid (ALA). In this study, the pharmacological activities including anti-tussive, expectorant and anti-inflammatory effect of PSO were performed. Furthermore, the 90-day sub-chronic oral toxicity with a 30 day recovery period was evaluated in Wistar rats. RESULTS: The pharmacological studies demonstrated that PSO inhibited cough frequency induced by capsaicine in mice. PSO also inhibited the leukotriene B4 (LTB4) release from the calcium ionophore A23187-induced polymorphonuclear neutrophils (PMNs) to some extent. In this sub-chronic toxicity study, mortality, clinical signs, body weight, food consumption, hematology, serum biochemistry, urinalysis, organ weight, necropsy, and histopathology were used to evaluate the toxicity of PSO. Lower body weight and various negative impacts on liver related parameters without histopathological lesion were observed in the 16 g kg-1 groups. No clinically significant changes were discovered in the 4 g kg-1 group during the test period. CONCLUSION: In summary, PSO exhibited anti-tussive and anti-inflammatory activities in vivo and in vitro. These sub-chronic toxicity studies inferred that the 'no-observed adverse effect level' (NOAEL) of PSO in Wistar rats was determined to be 4 g kg-1 . These results may provide a safety profile and a valuable reference for the use of PSO. © 2020 Society of Chemical Industry.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Cough/drug therapy , alpha-Linolenic Acid/administration & dosage , Animals , Anti-Inflammatory Agents/adverse effects , Cough/immunology , Drug Evaluation, Preclinical , Female , Humans , Liver/drug effects , Male , Neutrophils/drug effects , Neutrophils/immunology , Plant Oils/administration & dosage , Plant Oils/adverse effects , Rats , Rats, Wistar , Toxicology , alpha-Linolenic Acid/adverse effects
3.
Phytochemistry ; 171: 112228, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31911265

ABSTRACT

A previously undescribed taraxerene-type triterpenoid possessing a class of rare natural taraxerene triterpenoid possessing skeleton with 14, 28-lactone, two undescribed oleane-type triterpenoids, and twenty-five known triterpenoids were isolated from Liquidambar formosana (Hamamelidaceae). The structures of undescribed compounds were determined on the basis of 1D and 2D NMR spectroscopic, HR-ESI-MS, and X-ray crystallographic data analysis. Among the isolates, ursolic acid, 3,6-dion-20(29)-lupen-28-oic acid, and 3-oxo-12α-hydroxyoleanan-28,13ß-olide induced a significant apoptosis in SMMC7721 cells in the flow cytometer experiment with apoptosis rates of 94.5%, 57.3% and 89.9% at 8.0 µM, respectively, exhibiting near equivalent apoptosis-inducing abilities to that positive drug taxol (apoptotic rate of 71.2% at 1.4 µM). Mechanism studies suggested that these three compounds could regulate the mitochondrial pathway by up-regulating the expressions of pro-apoptotic factors (Bad and Bax) and activating caspase-3 and caspase-9 to induce apoptosis. Further studies indicated that the pro-apoptotic effects of these three compounds were associated with PI3K-AKT pathway inhibition. Taken together, these studies provide evidence that triterpenoids from L. Fructus are promising candidates for the hepatocellular carcinoma therapy.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Liquidambar/chemistry , Phytochemicals/pharmacology , Protein Kinase Inhibitors/pharmacology , Triterpenes/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Humans , Phosphatidylinositol 3-Kinases/metabolism , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/isolation & purification , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Triterpenes/chemistry , Triterpenes/isolation & purification , Tumor Cells, Cultured
4.
Regul Toxicol Pharmacol ; 103: 229-236, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30703409

ABSTRACT

Perilla seeds are used as food and traditional medicine in China. This study aimed to investigate the toxicity profile of Perilla seed oil (PSO), which is the main constituent of Perilla seeds in rodents and Beagle dogs. No significant treatment-associated toxicity or mortality was observed at PSO dosages of up to 50 g/kg and 20 g/kg in KM mice and Wistar rats, respectively, suggesting that PSO was well tolerated by the experimental rodents. Sub-chronic oral toxicity of PSO was studied in dogs at doses of 3, 6 and 12 g/kg/d for 90 days followed by a 30 day recovery period. The results indicated that the body weight increased in all-dose groups more than control group, typical of animals on diets rich in fatty acids. Treatment-related side effects, including changes in hematology and serum biochemistry parameters, histopathology of liver and lymph glands, were observed in the high and moderate-dose dogs. However, these changes disappeared after the doses were withdrawn during the recovery period, except for alteration of liver in the high-dose group. In conclusion, the "no observed adverse effect level" (NOAEL) of oral administration of PSO for 90 days in Beagle dogs was considered to be 3 g/kg/d.


Subject(s)
Liver/drug effects , Lymph Nodes/drug effects , alpha-Linolenic Acid/administration & dosage , alpha-Linolenic Acid/toxicity , Administration, Oral , Animals , Dogs , Dose-Response Relationship, Drug , Female , Male , Mice , Mice, Inbred Strains , Plant Oils/administration & dosage , Plant Oils/toxicity , Rats , Rats, Wistar , Toxicity Tests, Subchronic
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