Shanzha Research Articles

Exploring the Molecular Mechanisms of Herbs in the Treatment of Hyperlipidemia Based on Network Pharmacology and Molecular Docking.

Many herbs have been shown to safely and successfully treat hyperlipidemia. However, the molecular mechanisms underlying their treatment remain unclear. In this study, 103 prescriptions for the treatment of hyperlipidemia containing 146 herbs were screened. Cluster analyses identified a core prescription comprising five herbs, namely, Crataegus pinnatifida (Shan Zha), Cassiae semen (Jue Ming Zi), Alisma orientale (Sam.) Juz. (Ze Xie), Salvia miltiorrhiza (Dan Shen), and Radix Polygoni Multiflori (He Shou Wu), in combination for the treatment of hyperlipidemia. Next, 9, 62, 5, 132, and 34 potential targets for each of the core herbs and a total of 512 hyperlipidemia-related protein targets were detected. Finally, 40 targets shared by core herbs and hyperlipidemia were identified. IL6, AKT1, IL1B, PTGS2, VEGFA, PPARG, and NOS3 were the seven proteins that were found to be most important in the treatment of hyperlipidemia. Interestingly, the Kyoto Encyclopedia of Genes and Genomes pathway indicated that these targets were mainly enriched in the lipid and atherosclerosis pathway and the cancer pathway. In addition, core target proteins such as AKT1, PTGS2, and PPARG have been demonstrated to play critical roles in hyperlipidemia and pancreatic cancer. Significant affinity between bioactive chemicals and proteins involved in cancer pathways was found by molecular docking. Molecular docking results showed that AKT1, PTGS2, and PPARG exhibited good binding ability with three bioactive chemicals, including 3-beta-hydroxymethyllenetanshiquinone, danshexinkum d, and physciondiglucoside. The treatment of hyperlipidemia by herbs may be mediated through the modulation of proteins associated with the cancer pathway. This study helps to provide a theoretical basis for future combined therapy for hyperlipidemia and cancer. [Figure: see text].

Effect of Shan Zha (Hawthorn or Crataegus) on gastrointestinal cancer: A network pharmacology and molecular docking study

BackgroundShan Zha (Hawthorn or Crataegus) is a traditional Chinese medicine (TCM) most commonly used for the treatment of hyperlipidemia. Gastrointestinal cancer is closely correlated with blood lipid levels. This study illustrates the potential anticancer effects of Shan Zha on gastrointestinal tumors based on network pharmacology and molecular docking. MethodsHawthorn's bioactive ingredients and drug targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine version 2.0 (TCMIP v2.0), and Herbal Ingredients' Targets Platform (HIT 2.0) databases. Validated disease targets of gastrointestinal cancer were obtained from the Therapeutic Targets Database (TTD) and HIT 2.0 databases. Protein–protein interaction analysis of intersecting genes was performed using the Search Tool for the Retrieval of Interacting Genes (STRING) database. The functions of these genes were further analyzed by performing gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking verification was performed using Molecular Operating Environment (MOE) software. ResultsFour main bioactive components were identified in Shan Zha. A total of 271 potential drug targets were identified, and 393 gastrointestinal-tumor targets were obtained. Through protein interaction analysis of intersecting targets, the main components of Shan Zha were found to interact more closely with proteins such as tumor protein p53 (TP53), AKT serine/threonine kinase 1 (AKT1), JUN proto-oncogene (JUN), interleukin 6 (IL6), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor A (VEGFA). KEGG pathway enrichment analysis showed a total of 127 pathways, mainly involving pathways in multiple types of cancer, the Phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway, and EGFR tyrosine kinase inhibitor resistance. Combined with The Cancer Genome Atlas (TCGA) differential analysis, key targets, including TP53, cyclin D1 (CCND1), EGFR, and VEGFA, were screened. Molecular docking results showed that quercetin and kaempferol had the good binding potential for TP53, CCND1, EGFR, and VEGFA. ConclusionThese findings suggest that Shan Zha exerts its effects on gastrointestinal cancers through a multitarget, multi-component, and a multi-pathway mechanism.

Anxiolytic and antidepressants’ effect of Crataegus pinnatifida (Shan Zha): biochemical mechanisms

Depression and anxiety disorders are highly prevalent. Selective serotonin reuptake inhibitors (SSRIs) are the current first-line treatment for depression, but they have pronounced limitations. Traditional Chinese medicine can serve as a safe and effective alternative to conventional drugs, particularly since many herbal remedies have already been approved for human use as food additives, making the transition from bench to bedside more efficient. We previously demonstrated that a novel herbal treatment (NHT) induces anxiolytic- and antidepressant-like effects. NHT consists of four herbs: Crataegus pinnatifida (Shan Zha), Triticum aestivum (Fu Xiao Mai), Lilium brownii (Baihe), and the fruit of Ziziphus jujuba (Da Zao). In the current study, we examined the antidepressant-like and anxiolytic-like activities of each individual herb on stressed mice and compared those to the effects of NHT and escitalopram. We show here that Shan Zha is sufficient to produce an anxiolytic and antidepressant-like effect similar to NHT or the escitalopram through activation of 5-HT1A receptor and an elevation in BDNF levels in the hippocampus and Pre-frontal cortex (PFC). Chronic treatment with Shan Zha did not alter serotonin transporter levels in the PFC, as opposed to escitalopram treatment. These results were confirmed in vitro, as none of the herbs blocked SERT activity in Xenopus oocytes. Notably, Shan Zha is sold as a nutritional supplement; thus, its transition to clinical trials can be easier. Once its efficacy and safety are substantiated, Shan Zha may serve as an alternative to conventional antidepressants.

A systems-based analysis to explore the multiple mechanisms of Shan Zha for treating human diseases.

Shan Zha has garnered increasing attention in the field of functional foods and medicines due to its widely reported healing effects. However, the potential mechanisms of Shan Zha for human health benefits have not been fully interpreted. Therefore, in the current study, a systems-based method that integrates ADME evaluation, target fishing, gene ontology enrichment analysis, network pharmacology, and pathway analysis is proposed to clarify the underlying pharmacological mechanisms of Shan Zha. As a result, 45 active components of Shan Zha that interacted with 161 protein targets were screened and identified. Moreover, gene ontology enrichment, network and pathway analysis indicated that Shan Zha is beneficial for the treatment of cardiovascular system diseases, digestive system diseases, immune system diseases, inflammatory diseases, cancer, and other diseases through multiple mechanisms. Our study not only proposed an integrated method to comprehensively elucidate the complicated mechanisms of Shan Zha for the treatment of various disorders at the system level, but also provided a reference approach for the mechanistic research of other functional foods.

Use of traditional Chinese medicine in patients with hyperlipidemia: A population-based study in Taiwan

Ethno-pharmacological relevanceChinese herbal products (CHPs) are commonly used in patients with hyperlipidemia in traditional Chinese medicine (TCM). Because hyperlipidemia and related disease are common issues worldwide, this study analyzed the prescription patterns and frequencies of CHPs for treating patients with hyperlipidemia in Taiwan. BackgroundTraditional Chinese medicine (TCM) has become popular as a therapy for controlling symptoms in patients with hyperlipidemia. This study aimed to analyze the prescription patterns of TCM for patients with hyperlipidemia in Taiwan. MethodsThe study population was recruited from a random-sampled cohort of 1,000,000 people from the National Health Insurance Research Database between 2003 and 2009. We identified 30,784 outpatient visits related with hyperlipidemia diagnosis and collected these medical records. Association rules of data mining were conducted to explore the co-prescription patterns for Chinese herbal products (CHPs). ResultsThe most commonly prescribed herbal formula for hyperlipidemia treatment was Xue-Fu-Zhu-Yu-Tang (16.1%), and Shan Zha (Crataegi fructus; 25.0%) was the most commonly prescribed single herb. The most commonly prescribed combination of an herbal formula and a single herb was Xue-Fu-Zhu-Yu-Tang and Dan Shen (Radix Salviae Miltiorrhizae), and the most commonly prescribed combination of couplet herbs was Dan Shen and Shan Zha. ConclusionXue-Fu-Zhu-Yu-Tang is the most frequently prescribed formula and is typically prescribed with Shan Zha, Dan Shen, and He Shou Wu for patients with hyperlipidemia. Clinical trials are warranted in future research to investigate the effects of the CHPs in terms of safety and efficacy and in particular to evaluate potential interactions with conventional treatments.

Experimental study on anti-atherosclerotic effect of compatibility of active components of Danshen and Shanzha

To investigate the effect of active components of Danshen and Shanzha of different matching proportions on atherosclerosis (AS), in the expectation of obtaining the optimum combination method. Atherosclerotic rats were fed with high fat diet, and injected with vitamin D3 and ovalbumin. Aqueous extracts of Danshen (DSA) and Shanzha (SZA) and lipophilic extracts of danshen (DSL) were adopted for a low, medium and high-dose orthogonal experiment, to observe the effect of their different matching proportions on lipid level, oxidative stress, endothelial function and inflammatory reaction. The principal component analysis and cluster analysis were adopted for the multi-objective optimization of experimental results. Compared with the model group, all of samples with different proportions of DSA, DSL and SZA showed effect in lowering lipid level, scavenging free radicals, reducing endothelial dysfunction and inhibiting inflammation. According to the variance analysis, DSA2-SZA2-DSL1, DSA3-SZA2-DSL1, DSA3-SZA3 -DSL3 and DSA3-SZA1-DSL1 were the optimal proportions for lowering lipid level, scavenging free radicals, reducing endothelial dysfunction and inhibiting inflammation, respectively. According to the results of the multi-objective optimization, DSA2-SZA1-DSL2 was the optimal proportions of anti-AS. All of active components of Danshen and Shanzha of different matching proportions show the anti-AS effect in rats to varying degrees, but with different focus in different matching proportions.

Cholesterol lowering and vascular protective effects of ethanolic extract of dried fruit of Crataegus pinnatifida, hawthorn (Shan Zha), in diet-induced hypercholesterolaemic rat model

Consumption of functional foods for managing plasma cholesterol level has gained acceptance globally. The hypocholesterolaemic and vascular protective effects of the dried fruit of Crataegus pinnatifida, hawthorn (Shan Zha), were investigated in rats fed with normal diet, high cholesterol diet (HCD) or HCD plus Shan Zha 80% ethanolic extract treatment (30 or 100mg/kg/day, p.o.) for 4weeks. Shan Zha extract markedly reversed the increased plasma total cholesterol and high density lipoprotein cholesterol induced by HCD with a dose-dependent improvement on the atherogenic index. It also demonstrated good hepatoprotective function by reducing lipid content in the liver. The blunted endothelium-mediated aortic relaxation in HCD-fed rats was restored by high dosage of Shan Zha extract treatment. The current results showed that Shan Zha extract could provide its cholesterol lowering effect by up-regulating hepatic CYP7A1 mRNA expression which leads to enhanced bile acid biosynthesis. It is postulated that the hypocholesterolaemic effect is the primary beneficial effect given by Shan Zha extract; it then leads to other secondary beneficial effects such as vascular protective and hepatoprotective functions. Thus, Shan Zha extract could provide an overall improvement on the hepatic and vascular systems that may be important in relieving hypercholesterolaemia-related complications.

Development of the origin and application of shanza in ancient and modern

Shanzha is a popular Chinese herbal medicine and originally recorded in Xin Xiu Ben Cao. It was derivered form fruit of Crataegus cuneata Sieb. et Zucc form Tang dynasties until modern time. Present day, Shanzha has been recommended form fruit of Crataegus pinnatifida Bge. and C. pinnatifida Bge. var. major N.E.Br. in Chinese Pharmacopoeia. It can be seen C. cuneata has been used over 2000 years in China, so it has excellent production for using treatment. In Tang and Song dynasties, people thought Shanzha has cool nature and acid flavour, and used it in management of diagnostic criteria and principles. After Yuan dynasties, people have thought Shanzha has warm nature and acid-sweet flavour. Today, Shanzha is primarily used to remedy disease in digestive system and cardiovascular system. Through analysising Materia Medica (Ben Cao), we can find that the production and application of Shanzha is a changing process in history.

Consumption of dried fruit of Crataegus pinnatifida (hawthorn) suppresses high-cholesterol diet-induced hypercholesterolemia in rats

The hypocholesterolemic and atheroscleroprotective potentials of dietary consumption of hawthorn (dried fruit of Crataegus pinnatifida, Shan Zha) were investigated by monitoring plasma lipid profiles and aortic relaxation in Sprague–Dawley rats fed with either normal diet, high-cholesterol diet (HCD) or HCD supplemented with hawthorn powder (2%, w/w) (4 weeks). In HCD-fed rats, an increased plasma total cholesterol and LDL-cholesterol with a decreased HDL-cholesterol was observed, and consumption of hawthorn markedly suppressed the elevated total cholesterol and LDL-lipoprotein levels plus an increased HDL-cholesterol level. The blunted acetylcholine-induced, endothelium-dependent relaxation of isolated aortas of HCD-fed rats was improved by hawthorn. The development of fatty liver, an increased nitric oxide synthase (NOS) activity and an elevated oxidative stress (as estimated by the attenuated levels of anti-oxidant enzymes) associated with HCD were attenuated by hawthorn. Thus, the results demonstrated that hawthorn consumption provides overall beneficial effects on reversing HCD associated detrimental changes.

Antioxidant Activity of Traditional Chinese Medicinal Herbs

Traditional Chinese medicinal herbs have been used for thousands of years to treat numerous ailments. In recent years, these herbs have been the focus of attention due to their medicinal and pharmacological benefits. In the present study, 25 types of herbs commonly used in Chinese medicinal culinary diets were quantitatively investigated for their various antioxidant activities. Using the 1,1-diphenyl-2- picrylhydrazyl high pressure liquid chromatography and 2´-deoxyguanosine oxidation methods, the highest antioxidant activity was found in chrysanthemum (Ju Hua), followed by hawthorn (Shan Zha), licorice root (Gan Cao), hibiscus (Luo Shen Hua), cassia seed (Jue Ming Zi) and Chinese wolfberry (Gou Gi), while poria (Fu Ling) and adlay (Yi Yi Ren) contained the lowest antioxidant activity. The same trend was also observed for total phenolic content using the Folin-Ciocalteu method. Ascorbic acid and tocopherol were only detected in trace amounts, suggesting that phenolic compounds may be the main contributors to herbal antioxidant activities.

Combination of Wu Lin San and Shan Zha ameliorates substance P-induced hyperactive bladder via the inhibition of neutrophil NADPH oxidase activity

Substance P (SP) via neurokinin type 1 receptor activates leukocytes to produce burst release of reactive oxygen species (ROS) and increases leukocytes adhesion to the vessels in the inflamed bladder. Activation of neutrophil nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity may contribute to the neutrophil ROS production. We explored the therapeutic effect of traditional Chinese formula for urinary dysfunction, Wu Lin San (WLS), and a modified formula WLS plus Shan Zha (WLSSZ) on SP-induced bladder hyperactivity. We evaluated WLS, Shan Zha, and WLSSZ effect on neutrophils NADPH oxidase activity in SP-stimulated neutrophils in vitro, and isovolumetric cystometrogram and ROS activity in vivo in anesthetized rat bladder with SP stimulation. Our results showed that WLS, Shan Zha, and WLSSZ inhibited SP-induced NADPH oxidase activity in an order WLSSZ > Shan Zha > WLS. Exogenous SP enhanced systemic vasodilation, bladder hyperactivity and bladder ROS. One week of oral administration of WLS or WLSSZ significantly reduced SP-induced bladder ROS amount and leukocyte accumulation and ameliorated the hyperactive bladder response. The therapeutic action was better in WLSSZ than in WLS. Our results indicate that a modified formula Wu Lin San plus Shan Zha can potentially ameliorate SP-induced neurogenic inflammation possibly via the inhibition of leukocyte NADPH oxidase activity.

Hawthorn (shan zha) drink and its lowering effect on blood lipid levels in humans and rats.

Hawthorn (shan zha) drink and its lowering effect on blood lipid levels in humans and rats.