Open Access
Open access
Chinese Medicine, volume 16, issue 1, publication number 99

A network pharmacology-based approach to explore the active ingredients and molecular mechanism of Lei-gong-gen formula granule on a spontaneously hypertensive rat model

Qiaofeng Li 1, 2
Taijin Lan 3
Songhua He 4
Weiwei Chen 5, 6
Xiaolan Li 1, 2
WEIQUAN ZHANG 1, 2
Ying Liu 2, 7
Qiuping Zhang 2, 8
Xin Chen 1, 2
Yaoyao Han 1, 2
Zhiheng Su 1
Dan Zhu 1
Hongwei Guo 1, 2, 5
Show full list: 13 authors
Publication typeJournal Article
Publication date2021-10-09
Journal: Chinese Medicine
scimago Q1
SJR0.877
CiteScore7.9
Impact factor5.3
ISSN17498546, 21511918, 21511926
Pharmacology
Complementary and alternative medicine
Abstract
Lei-gong-gen formula granule (LFG) is a folk prescription derived from Zhuang nationality, the largest ethnic minority among 56 nationalities in China. It consists of three herbs, namely Eclipta prostrata (L.) L., Smilax glabra Roxb, and Centella asiatica (L.) Urb. It has been widely used as health protection tea for hundreds of years to prevent hypertension in Guangxi Zhuang Autonomous Region. The purpose of this study is to validate the antihypertensive effect of LFG on the spontaneously hypertensive rat (SHR) model, and to further identify the effective components and anti-hypertension mechanism of LFG. The effects of LFG on blood pressure, body weight, and heart rate were investigated in vivo using the SHR model. The levels of NO, ANG II, and ET-1 in the serum were measured, and pathological changes in the heart were examined by H&E staining. The main active components of LFG, their corresponding targets, and hypertension associated pathways were discerned through network pharmacology analysis based on the Traditional Chinese Medicine Systems Pharmacology (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID), and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Then the predicted results were further verified by molecular biology experiments such as RT-qPCR and western blot. Additionally, the potential active compounds were predicted by molecular docking technology, and the chemical constituents of LFG were analyzed and identified by UPLC-QTOF/MS technology. Finally, an in vitro assay was performed to investigate the protective effects of potential active compounds against hydrogen peroxide (H2O2) induced oxidative damage in human umbilical vein endothelial cells (HUVEC). LFG could effectively reduce blood pressure and increase serum NO content in SHR model. Histological results showed that LFG could ameliorate pathological changes such as cardiac hypertrophy and interstitial inflammation. From network pharmacology analysis, 53 candidate active compounds of LFG were collected, which linked to 765 potential targets, and 828 hypertension associated targets were retrieved, from which 12 overlapped targets both related to candidate active compounds from LFG and hypertension were screened and used as the potential targets of LFG on antihypertensive effect. The molecular biology experiments of the 12 overlapped targets showed that LFG could upregulate the mRNA and protein expressions of NOS3 and proto-oncogene tyrosine-protein kinase SRC (SRC) in the thoracic aorta. Pathway enrichment analysis showed that the PI3K-AKT signaling pathway was closely related to the expression of NOS3 and SRC. Moreover, western blot results showed that LFG significantly increased the protein expression levels of PI3K and phosphorylated AKT in SHR model, suggesting that LFG may active the PI3K-AKT signaling pathway to decrease hypertension. Molecular docking study further supported that p-hydroxybenzoic acid, cedar acid, shikimic acid, salicylic acid, nicotinic acid, linalool, and histidine can be well binding with NOS3, SRC, PI3K, and AKT. UPLC-QTOF/MS analysis confirmed that p-hydroxybenzoic acid, shikimic acid, salicylic acid, and nicotinic acid existed in LFG. Pre-treatment of HUVEC with nicotinic acid could alleviate the effect on cell viability induced by H2O2 and increase the NO level in cell supernatants. LFG can reduce the blood pressure in SHR model, which might be attributed to increasing the NO level in serum for promoting vasodilation via upregulating SRC expression level and activating the PI3K-AKT-NOS3 signaling pathway. Nicotinic acid might be the potential compound for LFG antihypertensive effect.
Lan T., Li Q., Chang M., Yin C., Zhu D., Wu Z., Li X., Zhang W., Yue B., Shi J., Yuan H., Su Z., Guo H.
Journal of Ethnopharmacology scimago Q1 wos Q1
2020-10-01 citations by CoLab: 20 Abstract  
Ethnopharmacological relevance Lei-gong-gen formula granule (LFG) is a folk prescription derived from Zhuang nationality, the largest ethnic minority among the 56 nationalities in China. It is composed of three herbs, namely Centella asiatica (L.) Urb., Eclipta prostrata (L.) L., Smilax glabra Roxb. It has been widely used as health protection tea for many years to prevent cardiovascular and cerebrovascular diseases such as hyperlipidemia and hypertension. Aim of the study This study validated the lipid-lowering effect of LFG in a hyperlipidemia rat model. Then we employed network pharmacology and molecular biological approach to identify the active ingredients of LFG, corresponding targets, and its anti-hyperlipidemia mechanisms. Materials and methods Hyperlipidemia rat model was established by feeding male Sprague-Dawley rats with high-fat diet for two weeks. LFG (two doses of 10 and 20 g/kg) was administered orally to hyperlipidemia rat model for 4 weeks, twice per day. Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) were monitored in rats pre and post-treatment. Hematoxylin-eosin staining was applied to observe the pathology and lipid accumulation of liver. We then performed network pharmacology analysis to predict the ingredients, their associated targets, and hyperlipidemia associated targets. Pathway analysis with significant genes was carried out using KEGG pathway. These genes and proteins intersectioned between compound targets and hyperlipidemia targets were further verified with samples from hyperlipidemia rats treated with LFG using Real-time RT-PCR and Western Blot. Results LFG attenuated hyperlipidemia in rat model, and this was characterized with decreased serum levels of TC, LDL-C, liver wet weight, and liver index. LFG alleviated the hepatic steatosis in hyperlipidemia rats. Network pharmacology analysis identified 53 bioactive ingredients from LFG formula (three herbs), which link to 765 potential targets. 53 hyperlipidemia associated genes were retrieved from public databases. There were 10 common genes between ingredients-targets and hyperlipidemia associated genes, which linked to 20 bioactive ingredients. Among these 10 genes, 3 of them were validated to be involved in LFG's anti-hyperlipidemia effect using Real-time RT-PCR, namely ADRB2 encoding beta-2 adrenergic receptor, NOS3 encoding nitric oxide synthase 3, LDLR encoding low-density lipoprotein receptor. The cGMP-PKG signaling pathway was enriched for hyperlipidemia after pharmacology network analysis with ADRB2, NOS3, and LDLR. Interestingly, expression of cGMP-dependent protein kinase (PKG) was downregulated in hyperlipidemia rat after LFG treatment. Molecular docking study further supported that ferulic acid, histidine, p-hydroxybenzoic acid, and linalool were potential active ingredients for LFG's anti-hyperlipidemia effect. LC-MS/MS analysis confirmed that ferulic acid and p-hydroxybenzoic acid were active ingredients of LFG. Conclusion LFG exhibited the lipid-lowering effect, which might be attributed to downregulating ADRB2 and NOS3, and upregulating LDLR through the cGMP-PKG signaling pathway in hyperlipidemia rat. Ferulic acid and p-hydroxybenzoic acid might be the underlying active ingredients which affect the potential targets for their anti-hyperlipidemia effect.
Wu W., Yang S., Liu P., Yin L., Gong Q., Zhu W.
Frontiers in Pharmacology scimago Q1 wos Q1 Open Access
2020-03-24 citations by CoLab: 26 PDF Abstract  
Hypertension is a clinical cardiovascular syndrome characterized by elevated systemic arterial pressure with or without multiple cardiovascular risk factors. Radix Pueraria (RP) has the effects of anti-myocardial ischemia, anti-arrhythmia, vasodilatation, blood pressure reduction, anti-inflammation and attenuating insulin resistance. Although RP can be effective for the treatment of hypertension, its active compounds, drug targets, and exact molecular mechanism are still unclear. In this study, systems pharmacology was used to analyze the active compounds, drug target genes and key pathways of RP in the treatment of hypertension. Thirteen active compounds and related information on RP were obtained from the TCMSP database, and 140 overlapping genes related to hypertension and drugs were obtained from the GeneCards and OMIM databases. A PPI network and a traditional Chinese medicine (TCM) comprehensive network (Drug-Compounds-Genes-Disease network) were constructed, and 2246 GO terms and 157 pathways were obtained by GO enrichment analysis and KEGG pathway enrichment analysis. Some important active compounds and targets were evaluated by in vitro experiments. This study shows that RP probably acts by influencing the proliferation module, apoptosis module, inflammation module, and others when treating hypertension. This study provides novel insights for researchers to systematically explore the mechanism of action of TCM.
Razali N.N., Ng C.T., Fong L.Y.
Planta Medica scimago Q2 wos Q2
2019-09-20 citations by CoLab: 53 Abstract  
Abstract Centella asiatica, a triterpene-rich medicinal herb, is traditionally used to treat various types of diseases including neurological, dermatological, and metabolic diseases. A few articles have previously reviewed a broad range of pharmacological activities of C. asiatica, but none of these reviews focuses on the use of C. asiatica in cardiovascular diseases. This review aims to summarize recent findings on protective effects of C. asiatica and its active constituents (asiatic acid, asiaticoside, madecassic acid, and madecassoside) in cardiovascular diseases. In addition, their beneficial effects on conditions associated with cardiovascular diseases were also reviewed. Articles were retrieved from electronic databases such as PubMed and Google Scholar using keywords “Centella asiatica,” “asiatic acid,” “asiaticoside,” “madecassic acid,” and “madecassoside.” The articles published between 2004 and 2018 that are related to the aforementioned topics were selected. A few clinical studies published beyond this period were also included. The results showed that C. asiatica and its active compounds possess potential therapeutic effects in cardiovascular diseases and cardiovascular disease-related conditions, as evidenced by numerous in silico, in vitro, in vivo, and clinical studies. C. asiatica and its triterpenes have been reported to exhibit cardioprotective, anti-atherosclerotic, antihypertensive, antihyperlipidemic, antidiabetic, antioxidant, and anti-inflammatory activities. In conclusion, more clinical and pharmacokinetic studies are needed to support the use of C. asiatica and its triterpenes as therapeutic agents for cardiovascular diseases. Besides, elucidation of the molecular pathways modulated by C. asiatica and its active constituents will help to understand the mechanisms underlying the cardioprotective action of C. asiatica.
Srinivasulu C., Ramgopal M., Ramanjaneyulu G., Anuradha C.M., Suresh Kumar C.
Biomedicine and Pharmacotherapy scimago Q1 wos Q1 Open Access
2018-12-01 citations by CoLab: 400 Abstract  
The use of phytochemicals in control of human diseases have been considerable public and scientific interest in current days. Syringic acid (SA), a phenolic compound often found in fruits and vegetables and which is synthesized via shikimic acid pathway in plants. It shows a wide range of therapeutic applications in prevention of diabetes, CVDs, cancer, cerebral ischemia; as well as it possess anti-oxidant, antimicrobial, anti-inflammatory, antiendotoxic, neuro and hepatoprotective activities. It has an effective free radical scavenger and alleviates the oxidative stress markers. The therapeutic property of SA is attributed by the presence of methoxy groups onto the aromatic ring at positions 3 and 5. The strong antioxidant activity of SA may confer its beneficial effects for human health. SA has the potential to modulate enzyme activity, protein dynamics and diverse transcription factors involved in diabetes, inflammation, cancer and angiogenesis. In vivo experimental data and histopathological studies on SA activity has delineated its possible therapeutic mechanisms. Besides usage in biomedical field, SA has greater industrial applications in bioremediation, photocatalytic ozonation, and laccase based catalysis. The present review deals about SA natural sources, biosynthesis, bioavailability, biomedical applications (in vivo and in vito. The review addresses basic information about molecular mechanisms, therapeutic and industrial potential of SA.
Szklarczyk D., Gable A.L., Lyon D., Junge A., Wyder S., Huerta-Cepas J., Simonovic M., Doncheva N.T., Morris J.H., Bork P., Jensen L.J., Mering C.
Nucleic Acids Research scimago Q1 wos Q1 Open Access
2018-11-22 citations by CoLab: 13120 PDF Abstract  
Proteins and their functional interactions form the backbone of the cellular machinery. Their connectivity network needs to be considered for the full understanding of biological phenomena, but the available information on protein-protein associations is incomplete and exhibits varying levels of annotation granularity and reliability. The STRING database aims to collect, score and integrate all publicly available sources of protein-protein interaction information, and to complement these with computational predictions. Its goal is to achieve a comprehensive and objective global network, including direct (physical) as well as indirect (functional) interactions. The latest version of STRING (11.0) more than doubles the number of organisms it covers, to 5090. The most important new feature is an option to upload entire, genome-wide datasets as input, allowing users to visualize subsets as interaction networks and to perform gene-set enrichment analysis on the entire input. For the enrichment analysis, STRING implements well-known classification systems such as Gene Ontology and KEGG, but also offers additional, new classification systems based on high-throughput text-mining as well as on a hierarchical clustering of the association network itself. The STRING resource is available online at https://string-db.org/.
Pereira I., Severino P., Santos A.C., Silva A.M., Souto E.B.
2018-11-01 citations by CoLab: 169 Abstract  
The medicinal properties of essential oils from aromatic plants are known since antiquity. Currently, the technological innovation enabled the reinvention of the ancient plant knowledge leading to the identification and extraction of organic compounds present in essential oils. These organic compounds belong mainly to the terpene group and are accountable for the wide range of bioactive properties attributed to essential oils. Linalool (C10H18O), so-called 3,7-dimethyl-1,6-octadien-3-ol, is a monoterpene alcohol broadly present as a major constituent of plant essential oils, particularly lavender and coriander. Linalool per se is non-toxic and, according to recent in vitro and in vivo scientific studies, it has demonstrated to have a comprehensive range of bioactive properties, which can be exploited for pharmaceutic and cosmetic applications. The present review focuses on the anti-inflammatory, anticancer, anti-hyperlipidemic, antimicrobial, antinoceptive, analgesic, anxiolytic, antidepressive and neuroprotective properties of linalool. The advantages of the loading in nanotechnology-based drug delivery systems, with the purpose of enhancing its bioactive properties are also discussed.
Vera-Aviles M., Vantana E., Kardinasari E., Koh N., Latunde-Dada G.
Pharmaceuticals scimago Q1 wos Q1 Open Access
2018-10-21 citations by CoLab: 63 PDF Abstract  
Anemia is a major health condition associated with chronic kidney disease (CKD). A key underlying cause of this disorder is iron deficiency. Although intravenous iron treatment can be beneficial in correcting CKD-associated anemia, surplus iron can be detrimental and cause complications. Excessive generation of reactive oxygen species (ROS), particularly by mitochondria, leads to tissue oxidation and damage to DNA, proteins, and lipids. Oxidative stress increase in CKD has been further implicated in the pathogenesis of vascular calcification. Iron supplementation leads to the availability of excess free iron that is toxic and generates ROS that is linked, in turn, to inflammation, endothelial dysfunction, and cardiovascular disease. Histidine is indispensable to uremic patients because of the tendency toward negative plasma histidine levels. Histidine-deficient diets predispose healthy subjects to anemia and accentuate anemia in chronic uremic patients. Histidine is essential in globin synthesis and erythropoiesis and has also been implicated in the enhancement of iron absorption from human diets. Studies have found that L-histidine exhibits antioxidant capabilities, such as scavenging free radicals and chelating divalent metal ions, hence the advocacy for its use in improving oxidative stress in CKD. The current review advances and discusses evidence for iron-induced toxicity in CKD and the mechanisms by which histidine exerts cytoprotective functions.
Camargo S.B., Simões L.O., Medeiros C.F., de Melo Jesus A., Fregoneze J.B., Evangelista A., Villarreal C.F., Araújo A.A., Quintans-Júnior L.J., Silva D.F.
Biochemical Pharmacology scimago Q1 wos Q1
2018-05-01 citations by CoLab: 26 Abstract  
Linalool (LIN) is a monoterpene alcohol present in some aromatic medicinal plants with biological activities that can impact cardiovascular diseases. This chemical class is highly volatile and β-cyclodextrin (β-CD) has been employed to improve the pharmacological properties of monoterpenes. Thus, the aim of this study was to evaluate the cardiovascular effects of LIN free focusing on the antihypertensive properties of this monoterpene and to study whether LIN, complexed in β-cyclodextrin (LIN-βCD) is able to improve the pharmacological activity of LIN. Spontaneously hypertensive rats (SHR) were randomly divided into 5 groups, each treated daily for 21 days, in the following manner: group 1 (vehicle solution); group 2 (captopril; 30 mg/kg/day); group 3 (LIN; 100 mg/kg/day); group 4 (LIN; 50 mg/kg/day) and group 5 (LIN/β-CD; 50 mg/kg/day). Daily body weight measurements were conducted and mean arterial pressure and heart rate were measured every 5 days. The mesenteric artery from treated animals was tested for phenylephrine and sodium nitroprusside (SNP) sensitivity. The SHR treated with vehicle demonstrated progressive increase in mean arterial pressure and captopril, a positive control, induced a significant decrease. After 21 days of treatment, the blood pressure of the SHR treated by (-)-LIN (100 mg/kg) was significantly reduced. In addition, various important cardiovascular parameters improved, including: the treatment with LIN prevented the development of cardiac hypertrophy, increased levels of the anti-inflammatory cytokine (IL-10), increased vasodilator responsiveness and reduced sensitivity to the sympathetic agonist. Furthermore, the inclusion complex containing LIN in β-CD produced a higher antihypertensive profile when compared with uncomplexed form. Taking together, our results suggested that LIN shown a potential antihypertensive effect and β-CD may be an important tool to improve the cardiovascular activity of LIN and other water-insoluble compounds.
Figueiredo-González M., Reboredo-Rodríguez P., González-Barreiro C., Simal-Gándara J., Valentão P., Carrasco-Pancorbo A., Andrade P.B., Cancho-Grande B.
Food Research International scimago Q1 wos Q1
2018-04-01 citations by CoLab: 34 Abstract  
In this work, phenol-rich extracts from 'Cornicabra' and 'Picual' virgin-olive oils (EVOOs) were examined, for the first time, to establish their capacity to inhibit key enzymes involved in Alzheimer's disease (AD) (acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and 5-lipoxygenase (LOX)), major depressive disorder (MDD) and Parkinson's disease (PD) (monoamine oxidases: hMAO-A and hMAO-B respectively), and diabetes mellitus (DM) (α-glucosidase and α-amylase). 'Cornicabra' displayed the best inhibitory activity against all enzymes, when compared to 'Picual': BuChE (IC50 = 156 ± 4 and 308 ± 33 mg mL-1), LOX (IC50 = 26 ± 0.5 and 37 ± 3 mg mL-1), hMAO-A (IC50 = 20 ± 2 and 37 ± 0.2 mg mL-1), hMAO-B (IC50 = 131 ± 7 and 215 ± 13 mg mL-1) and α-glucosidase (IC50 = 154 ± 17 and 251 ± 31 mg mL-1), respectively. The behaviour observed can be associated with the higher content of secoiridoids, lignans and phenolic acids in 'Cornicabra' EVOO.
Chung I., Rajakumar G., Lee J., Kim S., Thiruvengadam M.
2017-06-16 citations by CoLab: 44 Abstract  
Eclipta prostrata belongs to a family of medicinal plants (Asteraceae) and plays a role in the treatment of several diseases, including infectious hepatitis, snake venom poisoning, gastritis, and respiratory diseases such as a cough and asthma. A number of compounds, including thiophene derivatives, steroids, triterpenes, flavonoids, polyacetylenes, polypeptides, and coumestans, have been isolated from E. prostrata. The plant functional compounds can act as reducing agent in the field of nanoparticle synthesis. The extracts of E. prostrata are widely used for green biosynthesis of various metal and metal oxide nanoparticles, nanoparticles, which showed a potential for pharmaceutical, biotechnological, and biomedical applications. Establishment of a efficient in vitro regeneration and genetic transformation method of E. prostrata is a vital prerequisite for application of biotechnology in order to improve secondary metabolite yields. The present mini-review discusses its pharmacological profile, chemical constituents, biotechnological, and ethnomedical uses, mainly focusing on antimyotoxic, antihemorrhagic, antiproliferative, antioxidant, antitumor, antihyperglycemic, antidementia, antimicrobial, antihyperlipidemic, antivenom, anti-HIV, and larvicidal activities, so that the pharmaceutical potential of the plant can be better evaluated. The mini review, providing up-to-date phytochemical and other information on E. prostrata, will serve a reference for further studies.
Wang H., Liu C., Zhai J., Shang H.
2017-04-01 citations by CoLab: 8 Abstract  
Niuhuang Jiangya Preparation (NHJYP) is one of the most commonly used traditional Chinese patent medicines for essential hypertension (EH) in China. Our meta-analysis performed a systematic evaluation on the therapeutic efficacy and safety of NHJYP for EH.Systematic review and meta-analysis.PubMed, Embase, the Cochrane library, CNKI,VIP, Sinomed, and Wanfang Database were searched up to June 2015. Randomized controlled trials (RCTs) comparing NHJYP or combined with western antihypertensive drugs (WAD) versus WAD were included. Quality of each trial was assessed according to the Cochrane Reviewers' Handbook 5. 1.0. Statistical software (RevMan 5.3) was used for data analysis. The primary outcome was categorical or continuous blood pressure, and the secondary outcome was Traditional Chinese Medicine (TCM) syndrome.12 RCTs including 1651 cases were identified. The methodological quality of trials was low. Meta-analysis showed that, firstly, NHJYP used alone compared with WAD had no significant effect on BP reduction; however, subgroup analysis was used based on whether apply TCM diagnostic criteria in recruitment. It was suggested that, for population that applied TCM diagnostic criteria, RR=1.35,95% CI:1.17-1.56,P
Xiong X., Yang X., Duan L., Liu W., Zhang Y., Liu Y., Wang P., Li S., Li X.
Scientific Reports scimago Q1 wos Q1 Open Access
2017-02-22 citations by CoLab: 19 PDF Abstract  
Chinese herbal medicine Bu-Shen-Jiang-Ya decoction (BSJYD) is reported to be beneficial for hypertension. Over expression of extracellular signal regulated kinases (ERK) pathway plays an important role in left ventricular hypertrophy (LVH). This study aimed to observe effects of BSJYD on LVH in spontaneously hypertensive rats (SHRs) and explore its possible mechanism on regulation of ERK pathway. Sixty 12-week-old SHRs were randomly allocated into 5 groups: BSJYD high dose group, middle dose group, low dose group, captopril group, and control group. Besides, a control group of Wistar-Kyoto rats was established. All rats were treated for 8 weeks. Systolic blood pressure (SBP), heart rate (HR), pathology, and left ventricular mass index (LVMI) were measured. Western blotting and Real-time PCR were used to assess the expressions of BDNF, Ras, ERK1/2, and c-fox levels. SBP and HR were significantly decreased compared with the control group and LVMI was markedly improved by BSJYD treatment in a dose-dependent manner. BSJYD inhibited the expression of BDNF, Ras, ERK1/2, and c-fox mRNA in LVH. In conclusion, BSJYD suppressed hypertension-induced cardiac hypertrophy by inhibiting the expression of ERK pathway. These changes in gene expression may be a possible mechanism by which BSJYD provides myocardial protection from hypertension.
Li Y., Yang L., Wang L., Zhang M., Huang Z., Deng Q., Zhou M., Chen Z., Wang L.
2017-01-01 citations by CoLab: 155 Abstract  
Background Hypertension is a major cause of cardiovascular disease. Periodic nationwide surveys are essential for monitoring secular trend of hypertension and its control in population. We assessed prevalence of hypertension and related awareness, treatment and control rates in Chinese adults in 2013–14. Methods A nationally representative survey recruited 174,621 adults aged>18years from 31 provinces in mainland China between 2013 and 2014. Population-weighted prevalence of hypertension and related rates of awareness, treatment and control were calculated and compared by age, sex, region and other factors of interest. Results Overall, 27.8% of Chinese adults were hypertensive, with the adjusted prevalence higher in men than in women and increasing steeply with rising age. Of those with hypertension, 31.9% were previously diagnosed, of those diagnosed, 82.9% were treated, and of those treated, 34.6% had their blood pressure properly controlled, resulting in an overall control rates of 9.7% among those with hypertension. Despite similar prevalence, the awareness, treatment and control were much better in urban areas than in rural areas. Among hypertensive individuals, older age, higher levels of education or household income tended to be associated with better awareness, treatment and control rates. During 2013–14, 292 million adults in China had hypertension, representing an absolute increase of 139 million individuals since year 2002. Conclusions Among Chinese adults, more than one forth had hypertension and the prevalence has increased significantly during recent decades. Despite huge efforts, the levels of awareness, treatment and control rates of hypertension remain extremely low, foreshadowing substantial unnecessary disease burden.
Rabelo T.K., Guimarães A.G., Oliveira M.A., Gasparotto J., Serafini M.R., de Souza Araújo A.A., Quintans-Júnior L.J., Moreira J.C., Gelain D.P.
2016-10-01 citations by CoLab: 42 Abstract  
Shikimic acid (SA) is present in a wide variety of plants and microorganisms used in traditional and folk medicine and also is an essential starting material for the synthesis of the antiviral drug Oseltamivir (Tamiflu®). Some pharmacological actions observed in SA-enriched products include antioxidant and anti-inflammatory activities. Here, we investigated the anti-inflammatory and antinociceptive actions of isolated SA.RAW 264.7 macrophage cells were treated with bacterial LPS (1μg/mL) and the effect of SA on the modulation of cell viability, nitric oxide (NO) production, TNF-α, and IL-1β content and MAPK (ERK1/2 and p38) activation was evaluated. Besides, the anti-hyperalgesic actions of SA on in vivo model of mechanical hyperalgesia induced by carrageenan (CG), dopamine (DA), TNF-α and prostaglandin (PGE2) were assessed.In RAW 264.7 cells, SA suppressed LPS-induced decrease in cell viability and nitrite accumulation to control values and inhibited up-regulation of TNF-α (65%) and IL-1β (39%). These effects may be mediated at least in part by inhibition of LPS-induced ERK 1/2 (22%) and p38 (17%) phosphorylation. In mice, SA at 50, 100, and 200mg/kg decreased formalin-induced nociceptive behavior (around 50%) and inhibited the inflammatory nociception induced by TNF-α and PGE2 (50 to 75% each). Moreover, SA (100 and 200mg/kg) significantly attenuated the mechanical hyperalgesia induced by CG and DA (25 to 40% each).These results indicate that SA presents anti-inflammatory actions with potential for development of drugs to treat pro-inflammatory and painful conditions.
Liu Z., Guo F., Wang Y., Li C., Zhang X., Li H., Diao L., Gu J., Wang W., Li D., He F.
Scientific Reports scimago Q1 wos Q1 Open Access
2016-02-16 citations by CoLab: 554 PDF Abstract  
Traditional Chinese Medicine (TCM), with a history of thousands of years of clinical practice, is gaining more and more attention and application worldwide. And TCM-based new drug development, especially for the treatment of complex diseases is promising. However, owing to the TCM’s diverse ingredients and their complex interaction with human body, it is still quite difficult to uncover its molecular mechanism, which greatly hinders the TCM modernization and internationalization. Here we developed the first online Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM). Its main functions include 1) TCM ingredients’ target prediction; 2) functional analyses of targets including biological pathway, Gene Ontology functional term and disease enrichment analyses; 3) the visualization of ingredient-target-pathway/disease association network and KEGG biological pathway with highlighted targets; 4) comparison analysis of multiple TCMs. Finally, we applied BATMAN-TCM to Qishen Yiqi dripping Pill (QSYQ) and combined with subsequent experimental validation to reveal the functions of renin-angiotensin system responsible for QSYQ’s cardioprotective effects for the first time. BATMAN-TCM will contribute to the understanding of the “multi-component, multi-target and multi-pathway” combinational therapeutic mechanism of TCM and provide valuable clues for subsequent experimental validation, accelerating the elucidation of TCM’s molecular mechanism. BATMAN-TCM is available at http://bionet.ncpsb.org/batman-tcm .
Li X., Sheng J., Zhang X., Liu Y.
Agronomy scimago Q1 wos Q1 Open Access
2025-01-22 citations by CoLab: 0 PDF Abstract  
The harvesting age is a critical factor influencing the quality of medicinal crops, as it significantly affects the content of active compounds and clinical efficacy, which vary across different cultivation years. This study aims to clarify the growth and development patterns of wild-simulated and cultivated Astragalus mongholicus at different ages and provide theoretical and practical guidance for determining its optimal harvesting age. The morphological indicators, photosynthetic performance, stress resistance enzyme activities, medicinal compounds, and yields of Astragalus mongholicus cultivated and wild-simulated for one, two, three, and four years were analyzed. Results showed that the harvesting age influenced the various measurement indicators of wild-simulated Astragalus mongholicus. The underground growth of the two-year-old plants was the most vigorous, with a stronger photosynthetic capacity and the highest content of calycosin-7-O-glucoside. Both two-year-old and three-year-old plants exhibited higher superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) enzyme activities. The three-year-old plants had the highest astragaloside IV content and the greatest economic benefit. Considering both the quality of the medicinal material and the economic returns, this study suggests that the optimal harvesting age for wild-simulated cultivated Astragalus mongholicus in Inner Mongolia is three years, though harvesting at two years may also be feasible under practical conditions.
Zhang Q., Huang Q., Cheng Z., Xue W., Liu S., Liao Y., Li X., Chen X., Han Y., Zhu D., Su Z., Yang X., Luo Z., Guo H.
2025-01-22 citations by CoLab: 0
Li H., Li J., Wang X., Zeng M., Wu Y., Chen Y., Kong C., Chen K., Wu J., Mo Z., Zhang J., Liu C.
Frontiers in Pharmacology scimago Q1 wos Q1 Open Access
2024-11-28 citations by CoLab: 0 PDF Abstract  
BackgroundGoutengsan (GTS) is a traditional Chinese medicine formula that can improve multiple nervous system diseases, such as methamphetamine (MA) dependence. However, the mechanism how GTS treats MA dependence remains unclear. This study was aimed to investigate the action mechanism of GTS on MA dependence using network pharmacology, in vivo/in vitro experimental validation, pharmacokinetics, and tissue distribution in the brain.Materials and MethodsThe bioactive ingredients from GTS and possible targeted genes for treating MA dependence were predicted using network pharmacology. The binding of key components of GTS to the predicted proteins was studied using molecular docking, and the key components were verified by HPLC. The effects of GTS on an MA-induced model in rats and SH-SY5Y cells were studied. The regulatory effects of GTS on the expressions of predicted MAPK pathway-related proteins in rat brain tissues and SH-SY5Y cells were validated. Furthermore, the plasma exposure and brain tissue distribution of GTS ingredients for MA dependence treatment and MAPK pathway regulation were studied in mice.ResultsNetwork pharmacology screened 53 active ingredients, and 287 potential targets of GTS, and showed the MAPK pathway was among the most relevant pathways. Molecular docking showed that key active ingredients (e.g., 6-gingerol, liquiritin and rhynchophylline) bound strongly with MAPK core targets, such as MAPK3, and MAPK8. Five compounds of GTS were detected by HPLC, including 6-gingerol, chlorogenic acid, liquiritin, 5-o-methylviscumaboloside and hesperidin. GTS had a therapeutic effect on MA-dependent rats, and reduced hippocampal CA1 damage and relative expressions of p-MAPK3/MAPK3, p-MAPK8/MAPK8 in brain tissues induced by MA. GTS counteracted aberrant alterations in cAMP, 5-TH and cellular morphology induced by MA induction and exerts therapeutic effects on MA-induced SH-SY5Y cell models. GTS also can antagonize the high expressions of MAPK-related proteins in MA-induced SH-SY5Y cells. Pharmacokinetic experiment revealed the four ingredients of GTS (e.g., chlorogenic acid, 5-o-methylviscumaboloside, hesperidin and rhynchophylline) were exposed in the plasma and brain, which demonstrates its pharmacological effect on MA dependence.ConclusionGTS treats MA dependence by regulating the MAPK pathway via multiple bioactive ingredients. The network pharmacology, experimental validation and pharmacokinetics integrated strategy is efficient in discovering the key pharmacological mechanism of herbal formulae.
Xue Q., Liu C., Li Y.
Molecular Medicine scimago Q1 wos Q1 Open Access
2024-11-26 citations by CoLab: 0 PDF Abstract  
Abstract Background Hypertension is a leading risk factor for disability and deaths worldwide. Evidence indicates that alpha-mangostin(α-MG) can reduce blood pressure and improve target organ damage. Nonetheless, its pharmacological targets and potential mechanisms of action remain inadequately elucidated. Method We used SwissTargetPrediction to identify α-MG’s drug targets and DisGeNET, GeneCards, CTD, and GEO databases for hypertension-related targets, and then determined antihypertensive therapeutic targets of α-MG by intersecting these targets. GO functional enrichment analysis, KEGG pathway analysis, and disease association analysis were conducted using the DAVID database and R package “clusterprofile”, visualized with Cytoscape software. The binding affinity of α-MG to identified targets was confirmed through molecular docking using Autodock Vina v.1.2.2 software. The impact of α-MG on target genes was validated using an Angiotensin II-induced hypertensive mouse model and RT-qPCR. Results A total of 51 potential antihypertensive therapeutic targets for α-MG were identified by intersecting 109 drug targets with 821 disease targets. Furthermore, 10 cellular component terms, 10 disease terms, and the top 20 enriched biological processes, molecular functions, and KEGG pathways related to α-MG’s antihypertensive effects were documented. Molecular docking studies indicated a strong binding affinity of α-MG with the HSP90AA1 domain. In Ang II-induced hypertensive mice aorta, treatment with α-MG effectively reversed the aberrant mRNA expression of TNF, HSP90AA1, NFKB1, PPARG, SIRT1, PTGS2, and RELA. Conclusion Our analyses showed that TNF, HSP90AA1, NFKB1, PPARG, SIRT1, PTGS2, and RELA might be α-MG’s potential therapeutic targets for hypertension, laying groundwork for further investigation into its pharmacological mechanisms and clinical uses.
Zhang Z., Xie H., Farag M.A., Li Z., Wu Q., Shao P.
Food Science and Human Wellness scimago Q1 wos Q1 Open Access
2024-11-01 citations by CoLab: 0 Abstract  
Gastric ulcer is a widespread disease caused by various etiologies. Dendrobium officinale flowers exert several health benefits owing to their rich flavonoid content. In this study, protective effects and possible action mechanisms of D. officinale flowers’ flavonoid enriched extract (DOFF) were assessed against gastric ulcer. The result of sodium nitrite-aluminum nitrate colorimetry showed that 52.34% of the total extractive was flavonoid, and ultra-high performance liquid chromatography time of flight mass spectrometer (UPLC-Q-TOF/MS) revealed the presence of 28 components in DOFF of which 14 belonged to flavonoids. In addition, in vivo assay revealed DOFF potential in reducing the formation of ethanol-induced gastric mucosal lesions, with drop-in ulcer index from 64.3 to 32.0. Similar results were revealed in human gastric mucosal epithelia cells (GES-1), with cells’ viability to increase from 27.2% to 61.6% post DOFF administration. To analyzied the protect effect of DOFF, we used western blotting and immunofluorometric assay to revealed the expression levels of key proteins in cell pathways. The results showed that DOFF (320 μg/mL) could increase the level of oxidation marker protein (HO-1), apoptosis regulatory protein (Bcl-2) and autophagy marker (LC3β) by 50.84%, 43.85%, and 59.21% compared with ethanol- treated group respectively. Further analyzed of the mitochondrial activity and apoptosis pathway, we found that DOFF appeared to mitigate against ethanol-induced gastric mucosal injury via AMPK/mTOR/ULK1 and PI3K/AKT autophagy signaling pathways.
Lu Y., Xie X., Xin Q., Yuan R., Miao Y., Cong W., Chen K.
2024-07-03 citations by CoLab: 1 Abstract  
Hypertensive renal damage (HRD) is a major cause of end-stage renal disease. Among the causes of end-stage renal disease, HRD accounts for nearly 34% of the total number of cases. Antihypertensive treatment is primarily drug-based, but therapeutic efficacy is less effective and can have serious side effects. Chinese medicine (CM) has significant advantages in the treatment of HRD. CM is rich in various active ingredients and has the property of targeting multiple targets and channels. Therefore, the regulatory network of CM on disease is complex. A large number of CM have been employed to treat HRD, either as single applications or as part of compound formulations. The key possible mechanisms of CM for HRD include regulation of the renin-angiotensin-aldosterone system, antioxidation, anti-inflammation, rescue of endothelial function, regulation of vasoactive substance secretion and obesity-related factors, etc. This review summarized and discussed the recent advance in the basic research mechanisms of CM interventions for HRD and pointed out the challenges and future prospects.
Chen Y., Dong Y., Song L., Bai C., Wang B., Sa C.
2024-05-07 citations by CoLab: 2 PDF Abstract  
Leontopodium leontopodioides (Willd.) Beauv. (L. leontopodioides.) has been used to treat lung diseases in traditional Chinese medicine (TCM). However, a systematic analysis of its chemical components has not been reported so far. In this study, UPLC-Q-Orbitrap MS and GC-MS were applied to investigate the chemical composition of the water extracts and essential oils of L. leontopodioides. UPLC-Q-Orbitrap MS adopts a heating electrospray ionization source, collecting primary and secondary mass spectrometry data in positive and negative ions, respectively, and uses Compound Discoverer 3.2 software to analyze the collected raw data. As a result, a total of 39 compounds were identified from their high-resolution mass spectra in both positive and negative ionization modes, including 13 flavonoids and their glycosides, 15 phenolic acids, 4 oligosaccharides and glycosides, 4 pentacyclic triterpenoids, and 3 other compounds. Among them, 18 chemical components have not been reported in L. leontopodioides. In the GC-MS section, two common organic solvents (n-hexane and diethyl ether) were used to extract essential oils, and the mass spectra were recorded at 70 eV (electron impact) and scanned in the range of 35∼450 m/z. Compounds were identified using NIST (version 2017), and the peak area normalization method was used to calculate their relative amounts. Finally, 17 components were identified in the volatile oil extracted with n-hexane, accounting for 80.38% of the total volatile oil, including monoterpenoids, phenylpropene, fatty acids, and aliphatic hydrocarbons. In the volatile oil extracted with diethyl ether, 16 components were identified, accounting for 73.50% of the total volatile oil, including phenylpropene, aliphatic hydrocarbons, monoterpenoids, fatty acids, and esters. This study was the first to conduct a comprehensive analysis of the chemical composition of the L. leontopodioides water extract and its essential oil, and a comprehensive chemical composition spectrum was constructed, to lay a foundation for its further pharmacodynamic material basis and quality evaluation.
Guo S., Zhang Q., Li X., Yu X., Lan T., Zhang W., Han Y., Chen X., Yang X., Guo H.
Heliyon scimago Q1 wos Q1 Open Access
2024-04-15 citations by CoLab: 0 Abstract  
To explore the molecular mechanism of Aidi injection in the treatment of prostate cancer (PCa).
Bansal K., Bhati H., Vanshita, Bajpai M.
2024-03-01 citations by CoLab: 10 Abstract  
: Centella asiatica (L.) Urb. is an authentic herbal medicine that is frequently used in Southeast Asian regions and scientific investigations have demonstrated the benefits of Centella asiatica and its constituents in various health issues. The active constituents of Centella asiatica are pentacyclic triterpenoid (asiatic acid, adecassic acid, madecassoside, and asiaticoside) and saponins. : The study includes a thorough review of prior research findings of an assortment of sources is used to gather data on its therapeutic potential and novel delivery approaches of C. asiatica. This review outlines evidence-based recent updates on the potential therapeutic actions and various nanocarrier types that are employed to deliver the actives of Centella asiatica to address the issues of poor stability, limited bioavailability, and higher metabolism, providing a new way to utilize these bioactive as a first-line treatment for various disorders. : The findings revealed that C. asiatica possesses a broad array of therapeutic effects including anti-ulcer, anti-cancer, anti-diabetic, anti-osteoporotic, neuroprotective, antioxidant, cardioprotective, and anti-inflammatory activities. Further, various approaches have been examined to overcome these constraints with the development of novel carrier systems including nanoparticles, polymeric nanocarriers, transferosomes, nanoemulsions, nanosuspensions, liposomes, hydrogels, microneedles, and micelles. : The study involves the importance of C. asiatica as a potential natural resource with a wide range of traditional uses. Its medicinal properties, which include the ability to treat chronic illnesses like cancer as well as fight infections, emphasize the importance of this plant in modern medicine. Future studies should prioritize in vivo and in vitro clinical trials to broaden the understanding of the mechanism involved as well as the development of more advanced delivery approaches in order to improve its utilization in healthcare.
Wang P., Hao D., Xiong X.
Journal of Ethnopharmacology scimago Q1 wos Q1
2024-01-01 citations by CoLab: 3 Abstract  
Wuwei Jiangya decoction (WJD) is a traditional Chinese medicinal formula (Fangji) composed of Gastrodiae Rhizoma, Chuanxiong Rhizoma, Puerariae Lobatae Radix, Cyathulae Radix, and Achyranthis Bidentatae Radix, all of which have been verified to combat hypertension. However, the integrative “shot-gun” mechanism of WJD and its primary active ingredients are still unclear. To investigate the anti-hypertensive effects of WJD and its originating ingredients. Network-based degree distribution analysis combined with in vivo experiments were performed. A total of 144 active ingredients in WJD were identified to regulate 84 hypertension-related targets, which are mainly involved in blood pressure and blood vessel diameter regulation. However, for the anti-hypertension effects, “more does not mean better”. The majority (76%) of the hubs in the H-network were regulated by no more than four ingredients. We identified 16 primary ingredients that accounted for the therapeutic action against hypertension. For compatibility, the five herbs consistently focused on blood pressure, vascular diameter, and angiogenesis, with the renin-angiotensin system as a primary target. The characteristics of each herb were involved in processes such as lipid localization and oxidative stress, which interact to constitute the regulatory network targeting hypertension, its risk factors, and organ damage. In vivo, WJD significantly reduced systolic blood pressure (SBP), improved left ventricular mass index, and ameliorated cardiac hypertrophy and vascular injury by moderating the renin-angiotensin system via activating the ACE2/Ang-(1–7)/Mas signaling pathway. WJD can lower SBP and ameliorate cardiac hypertrophy and vascular injury through the ACE2/Ang-(1–7)/Mas pathway, thus providing new insights into the development of traditional Chinese medicine as a therapeutic agent for hypertension.
Yan Z., Zhao G., Lin Q., Zhuang G., Zhu J., Jin J.
Peptide Science scimago Q2 wos Q4
2023-10-19 citations by CoLab: 0 Abstract  
AbstractCarapax Trionycis is a traditional Chinese medicine and it has been clear that oligo‐peptides from Carapax Trionycis extract (CTP) are the main active substances for the treatment of liver diseases. However, little is known about the mechanism of CTP against liver fibrosis. Here, network pharmacology combined with molecular docking were performed to identify the in‐silico molecular mechanism and the potential targets for CTP to ameliorate liver fibrosis. We collected eight active peptides ingredients that published in public databases and predicted the targets. Liver fibrosis related genes were acquired from the GeneCards and DisGeNET platform. Then, we identified a total of 52 peptides‐liver fibrosis‐related genes. KEGG and GO enrichment analyses indicated that these targets are significantly enriched in relaxin signaling pathway, IL‐17 signaling pathway, TNF signaling pathway. We identified the top 10 genes with high centrality measures from the network by CytoHubba, including CASP3, AKT1, IL1B, MMP9, and PTGS2. The molecular docking between these hub genes and the corresponding CTP was performed in GRAMM and visualized by PyMOL. Our results provide an important reference and scientific basis for treating liver fibrosis with CTP.
Lin J., Wang Q., Zhong D., Zhang J., Yuan T., Wu H., Li B., Li S., Xie X., An D., Deng Y., Xian S., Xiong X., Yao K.
Frontiers in Pharmacology scimago Q1 wos Q1 Open Access
2023-07-10 citations by CoLab: 3 PDF Abstract  
Background: Hypertension, a major cardiovascular risk factor, severely impacts patients’ quality of life. Qiangli Dingxuan tablet (QDT) is a formally approved Chinese patent medicine, which has been widely used as an adjunctive treatment for hypertension. This study aimed to investigate the antihypertensive efficacy and safety of QDT combined with amlodipine besylate in patients with essential hypertension.Methods: In this randomized, double-blind, placebo-controlled, parallel-group, multicenter trial conducted in China, patients diagnosed with grade 1 to 2 essential hypertension were randomly assigned in a 1:1 to the treatment of QDT or placebo for 12 weeks, alongside their ongoing treatment with amlodipine besylate. The primary outcome was the change in office blood pressure (BP) from baseline to 12 weeks. In addition, safety analysis included the assessment of vital signs and laboratory values.Results: At baseline, 269 patients were randomly assigned to the QDT group (n = 133) or the placebo group (n = 136), and there were no significant differences in baseline characteristics between the two groups. The primary outcome based on the full analysis set from baseline to 12 weeks showed that the mean difference in the change of office systolic BP reduction between the two groups was 6.86 mmHg (95%CI, 4.84 to 8.88, p < 0.0001), for office diastolic BP, the mean difference in the change of office diastolic BP reduction between the two groups was 4.64 mmHg (95%CI, 3.10 to 6.18, p < 0.0001). In addition, traditional Chinese medicine symptom scores were significantly decreased in the QDT group compared with the placebo group. No severe adverse events attributable to QDT were reported.Conclusion: The combination of QDT and amlodipine besylate demonstrates superior efficacy compared to amlodipine besylate monotherapy in the management of essential hypertension. QDT shows potential as an adjunctive treatment for essential hypertension. However, further rigorous clinical trials are warranted to validate these findings.Clinical Trial Registration: [https://clinicaltrials.gov/study/NCT05521282?cond=NCT05521282&rank=1]; Identifier: [NCT05521282]

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