Panax ginseng C.A.Mey. is an adaptogenic plant traditionally used to enhance mental and physical capacities in cases of weakness, exhaustion, tiredness, or loss of concentration, and during recovery. According to ancient records, red ginseng root preparations enhance longevity with long-term intake. Recent pharmacokinetic studies of ginsenosides in humans and our in vitro study in neuronal cells suggest that ginsenosides are effective when their levels in blood is low—at concentrations from 10−6 to 10−18 M. In the present study, we compared the effects of red ginseng root preparation HRG80TM(HRG) at concentrations from 0.01 to 10,000 ng/mL with effects of white ginseng (WG) and purified ginsenosides Rb1, Rg3, Rg5 and Rk1 on gene expression in isolated hippocampal neurons. The aim of this study was to predict the effects of differently expressed genes on cellular and physiological functions in organismal disorders and diseases. Gene expression profiling was performed by transcriptome-wide mRNA microarray analyses in murine HT22 cells after treatment with ginseng preparations. Ingenuity pathway downstream/upstream analysis (IPA) was performed with datasets of significantly up- or downregulated genes, and expected effects on cellular function and disease were identified by IPA software. Ginsenosides Rb1, Rg3, Rg5, and Rk1 have substantially varied effects on gene expression profiles (signatures) and are different from signatures of HRG and WG. Furthermore, the signature of HRG is changed significantly with dilution from 10,000 to 0.01 ng/mL. Network pharmacological analyses of gene expression profiles showed that HRG exhibits predictable positive effects in neuroinflammation, senescence, apoptosis, and immune response, suggesting beneficial soft-acting effects in cancer, gastrointestinal, and endocrine systems diseases and disorders in a wide range of low concentrations in blood.

Network Pharmacology of Ginseng (Part II): The Differential Effects of Red Ginseng and Ginsenoside Rg5 in Cancer and Heart Diseases as Determined by Transcriptomics.

The distinct of chemical profiles of mountainous forest cultivated ginseng and garden ginseng based on ginsenosides and oligosaccharides

Abstract In China, traditional Chinese medicine (TCM) has been widely used for coronavirus infectious disease 2019 (COVID‐19) prevention, treatment, and recovery and has played a part in the battle against the disease. A variety of TCM treatments have been recommended for different stages of COVID‐19. But, to the best of our knowledge, a comprehensive database for storing and organizing anti‐COVID TCM treatments is still lacking. Herein, we developed TCM2COVID, a manually curated resource of anti‐COVID TCM formulas, natural products (NPs), and herbs. The current version of TCM2COVID (1) documents over 280 TCM formulas (including over 300 herbs) with detailed clinical evidence and therapeutic mechanism information; (2) records over 80 NPs with detailed potential therapeutic mechanisms; and (3) launches a useful web server for querying, analyzing and visualizing documented formulas similar to those supplied by the user (formula similarity analysis). In summary, TCM2COVD provides a user‐friendly and practical platform for documenting, querying, and browsing anti‐COVID TCM treatments, and will help in the development and elucidation of the mechanisms of action of new anti‐COVID TCM therapies to support the fight against the COVID‐19 epidemic. TCM2COVID is freely available at http://zhangy-lab.cn/tcm2covid/.

TCM2COVID: A resource of anti‐COVID‐19 traditional Chinese medicine with effects and mechanisms

Significance Huashi Baidu decoction (Q-14), a famous traditional Chinese medicine decoction for COVID-19, has good effects on SARS-CoV-2 RNA clearance, promoting lung lesion opacity absorption, reducing inflammation, and ameliorating flu-like symptoms based on a series of clinical trials, having potent antiviral and anti-inflammatory effects. However, due to the lack of systematic and in-depth research, little significant progress has been made in the study of TCMT-NDRD of HBF for COVID-19 management. Therefore, the aim of the current study was to identify key antiviral and anti-inflammatory bioactive compounds from HBF based on an integrative pharmacological strategy. These findings will greatly stimulate the traditional Chinese medicine theory-driven natural drug discovery against COVID-19 and promote the modern research of Chinese medicine.

Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19

In-depth research on the mechanism of food nutrition and bioactivity has always been a shortcoming. The main function of the food itself is to meet the nutritional needs of the human body, not the therapeutic effect. Therefore, its relatively modest biological activity makes it difficult to study in general pharmacological models. With the popularity of functional foods and the concept of dietary therapy, the development of information and multi-omics technology in food research, the mechanism research of food is also moving towards a more microscopic future. Network pharmacology has accumulated nearly 20 years of experience in the research of traditional Chinese medicine (TCM), among which there is no lack of TCMs for both medicinal and edible purposes. Based on the similarity in the "multi-component-multi-target" properties of food and TCM, we think that network pharmacology is applicable to the study of the complex mechanism of food. In this review, we review the development of network pharmacology, summarize its application in "medicine and food homology", and proposal the methodology based on food characteristics for the first time, thereby demonstrating its feasibility in food research. This article is protected by copyright. All rights reserved.

Application prospect of traditional Chinese medicine network pharmacology in food science research.

Panax ginseng C. A. Mey (PGCAM) is a herbaceous perennial belonging to the Araliaceae family, mainly including Mountain-Cultivated Ginseng (MCG) and Garden Ginseng (GG) on the market. We aimed to establish a rapid, accurate and effective method to distinguish 15-year-old MCG and GG using ultra-performance liquid chromatography-quadrupole time-of-flight-tandem mass spectrometry (UPLC-QTOF-MS/MS), and also explored the pharmacological mechanisms of the main components using the Integrative Pharmacology-based Network Computational Research Platform of Traditional Chinese Medicine (TCMIP V2.0; http://www.tcmip.cn/). Altogether, 23 potential quality markers were characterized to distinguish 15-year-old MCG and GG, including ginsenosides Ra2, Rg1, and Ra1, and malonyl-ginsenoside Ra3, etc. The contents of 19 constituents (mainly protopanaxadiol-type) were higher in MCG compared with that in GG, and four constituents (mainly carbohydrate compounds) were higher in GG. The 105 putative targets corresponding to 23 potential quality markers were mainly involved in 30 pathways, which could be divided into 10 models, such as immune regulation, systems (metabolic, nervous, cardiovascular, reproductive), blood-pressure regulation, as well as antitumor, antiaging, antibacterial and anti-inflammatory effects. Furthermore, the potential quality markers of MCG and GG could inhibit the proliferation of breast cancer by regulating the mRNA expression of PSA, S6K, MDM2, and P53 genes by acting on AR, MTOR, PI3K and other targets. The Integrative Pharmacology Strategy may provide an efficient way to identify chemical constituents and explore the pharmacological actions of TCM formulations.

/pdf/characterization-of-the-components-and-pharmacological-t7bogdfwhd.pdf

Characterization of the Components and Pharmacological Effects of Mountain-Cultivated Ginseng and Garden Ginseng Based on the Integrative Pharmacology Strategy.

SoFDA: an integrated web platform from syndrome ontology to network-based evaluation of disease-syndrome-formula associations for precision medicine.

Portulaca oleracea L., known as the "vegetable for long life," is an annual succulent herb that is widely distributed worldwide. Many clinical and experimental studies have demonstrated that purslane seed (MCXZ) can be used as an adjunctive and alternative therapy for the treatment of diabetes mellitus (DM). However, the underlying active constituents and pharmacological mechanisms through which MCXZ exerts effects in DM remain unclear. In the present study, we confirmed that MCXZ treatment resulted in hypoglycemic activity, lowering the fasting blood glucose and glycated hemoglobin levels in streptozotocin-induced diabetic mice. Then, ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry was used to systematically analyze the chemical profile of MCXZ, resulting in the identification of 84 constituents, including 31 organic acids and nine flavonoids. Finally, the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine was employed to analyze the key active components of MCXZ and the molecular mechanisms through which these components acted in DM. Ten key active compounds were identified based on the topological importance of their corresponding putative targets within the known DM-associated therapeutic target network of known MCXZ putative targets. Functionally, these candidate targets play critical anti-hyperlipidemia, anti-hyperglycemia, immunity regulation, and inflammatory roles involving DM-related pathways, such as the vascular endothelial growth factor (VEGF) signaling pathway and Fc gamma R-mediated phagocytosis, which indicated that MCXZ exhibited anti-diabetic activity through multi-faced actions.

/pdf/an-integrative-pharmacology-based-approach-for-evaluating-1buhszw9nv.pdf

An Integrative Pharmacology-Based Approach for Evaluating the Potential Effects of Purslane Seed in Diabetes Mellitus Treatment Using UHPLC-LTQ-Orbitrap and TCMIP V2.0.

Abstract Background Renal fibrosis is the late stage of many chronic kidney diseases (CKD). Clinically, there is almost no effective treatment for renal fibrosis except dialysis. Renshen Guben oral liquid (RSGB) is a Chinese patent medicine approved by National Medical Products Administration (NMPA), which is suitable for clinical patients with chronic nephritis. Currently, the chemical constituents of RSGB remains unclear, and its efficacy and mechanism on renal fibrosis have not been reported. Methods In our research, ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was employed to describe the chemical profile of RSGB, unilateral ureteral obstruction (UUO) model in mice was established to evaluate the beneficial effect of RSGB on renal fibrosis by biochemical indexes, HE and Masson staining. RNA sequencing and “constituents-targets-pathways” multi-dimensional network was established to mine the mechanisms of RSGB. Key targets were verified by quantitative real-time PCR (qRT-PCR) and western bolt (WB). Results A total of 201 constituents were identified or tentatively characterized, 15 of which were confirmed with standards. The number of triterpenes was the highest with 49, followed by phenols with 46. RSGB ameliorated the blood urea nitrogen (BUN) and serum creatinine (Scr) levels in serum, normalizing pathological structure of kidney tissue. RNA sequencing revealed that RSGB regulates 226 differential genes, which were involved in kidney development. According to the “constituents-targets-pathways” network, 26 key active constituents may mainly regulate the inflammatory immune system through 88 corresponding targets. qRT-PCR and WB results showed that RSGB inhibited the activation of the Tgfβ1/Smad2/3 pathway, Wnt4/β-Catenin pathway and NGFR/NF-κB pathway. Conclusions Overall, our study, for the first time, characterized 201 chemical constituents in RSGB, and 26 of them were screened out to alleviates renal fibrosis mainly through Tgfβ1/Smad2/3 pathway, Wnt4/β-catenin pathway and NGFR/NF-κB pathway, which may provide a new research strategy for research on the mechanism of traditional Chinese Medicine. 

/pdf/identification-of-the-main-chemical-constituents-and-20qo5p5j.pdf

Yuewen Qin

Papers

Characterization of the Components and Pharmacological Effects of Mountain-Cultivated Ginseng and Garden Ginseng Based on the Integrative Pharmacology Strategy.

SoFDA: an integrated web platform from syndrome ontology to network-based evaluation of disease-syndrome-formula associations for precision medicine.

An Integrative Pharmacology-Based Approach for Evaluating the Potential Effects of Purslane Seed in Diabetes Mellitus Treatment Using UHPLC-LTQ-Orbitrap and TCMIP V2.0.

Identification of the Main Chemical constituents and mechanism of Renshen Guben oral liquid against Renal Fibrosis