• NAFLD
• endoplasmic reticulum stress
• ginsenoside Rh2
• macrophage

• Humans
• Ginsenosides/pharmacology
• Apoptosis/drug effects
• Hepatocytes/drug effects
• Hepatocytes/metabolism
• Endoplasmic Reticulum Stress/drug effects
• Hep G2 Cells
• Macrophages/drug effects
• Macrophages/metabolism
• Non-alcoholic Fatty Liver Disease/drug therapy
• Non-alcoholic Fatty Liver Disease/metabolism
• Inflammation/drug therapy
• Lipid Metabolism/drug effects
• THP-1 Cells
• Thapsigargin
• Macrophage Activation/drug effects

• Red ginseng
• ZBP1
• cell death
• host defense
• influenza A virus

• Panax/chemistry
• Influenza A virus/drug effects
• Humans
• Cell Death/drug effects
• Antiviral Agents/pharmacology
• RNA-Binding Proteins/metabolism
• Viral Proteins/metabolism
• Viral Proteins/genetics
• Animals
• Plant Extracts/pharmacology
• Dogs
• Influenza, Human/virology
• Influenza, Human/drug therapy
• DNA-Binding Proteins/metabolism
• DNA-Binding Proteins/genetics
• Madin Darby Canine Kidney Cells
• A549 Cells

• Alkaloids
• Apoptosis
• Cancer
• Flavonoids
• Inflammation
• Natural products
• Terpenoids

• Humans
• Neoplasms/drug therapy
• Biological Products/therapeutic use
• Biological Products/pharmacology
• Animals
• Antineoplastic Agents, Phytogenic/therapeutic use
• Antineoplastic Agents, Phytogenic/pharmacology
• Antineoplastic Agents/therapeutic use

• (20S)-protopanaxadiol
• Cytochrome P450
• Drug interaction
• Ginsenoside
• Pharmacodynamics
• Pharmacokinetics
• Preclinical
• Prostate cancer
• Rh2

• Male
• Humans
• Ginsenosides/pharmacology
• Ginsenosides/therapeutic use
• Sapogenins/pharmacokinetics
• Sapogenins/therapeutic use
• Drug Interactions
• Prostatic Neoplasms/drug therapy
• Prostatic Neoplasms/metabolism
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use

• AD-1 and AD-2
• ROS
• anti-cancer
• apoptosis
• isomers

• Stat3/p53/NRF2 axis
• colorectal cancer
• ferroptosis
• ginsenoside Rh3
• pyroptosis

• Bioinformatics analysis
• Cell cycle
• Compound K
• Ginseng
• Prostate cancer

• Male
• Humans
• Ginsenosides/pharmacology
• Antineoplastic Agents/pharmacology
• Cell Cycle
• Prostatic Neoplasms/drug therapy
• Prostatic Neoplasms/genetics
• Cell Proliferation
• Cell Line, Tumor
• Membrane Proteins
• Protein-Tyrosine Kinases/pharmacology
• Protein Serine-Threonine Kinases

• Ginseng
• Luciferase expressing reporter gene
• On-surface adherent cell assay
• PPARγ and Cytotox CALUX®
• Saussurea costus

• Cell Line
• Chromatography
• Genes, Reporter
• Humans
• Luciferases
• Mass Spectrometry

• 2-Pyrazine-PPD
• 25-OH-PPD
• Apoptosis
• Endoplasmic reticulum stress
• Reactive oxygen species

• Chinese herb medicines
• Fibrosis
• Ginseng
• Ginsenosides
• Therapeutics

• 25-OH-PPD
• 4-XL-PPD
• Apoptosis
• Migratory and invasive
• Reactive oxygen species

Shenqi Fuzheng Injection (SFI) is a traditional Chinese medicine injection with anticancer properties and is mainly composed of ginseng and astragalus. Its efficacy has been confirmed in clinical trials, but the mechanism remains unclear. We investigated the effect of SFI on vascular endothelial growth factor (VEGF) gene expression in hepatocellular carcinoma (HCC) cells and identified its possible mechanism of synergistic effects when combined with the chemotherapeutic drug interferon (IFN-) α. An MTT assay was used to measure the inhibition effects of low-dose IFN-α (6000 IU) with or without SFI (0.5 g/L) on the HCC cell line MHCC97. VEGF-silenced MHCC97L-mir200 cell lines were prepared using lentiviral vectors and evaluated by real-time PCR to determine the inhibition effect. We examined MHCC97L-mir200 and MHCC97L cells by MTT assay, using IFN-α alone or in combination with SFI. The inhibition ratio of IFN-α (6000 IU) was -29.5%, while that for IFN-α (6000 IU) + SFI (0.5 g/L) was 17.0%, which was significantly higher than that for the IFN-α group (P < 0.01). The VEGF gene was silenced successfully in MHCC97-L cells. After interference of VEGF, the inhibition by SFI and IFN-α in MHCC97L-mir200 did not differ from that in MHCC97-L cells (P > 0.05). SFI can reduce the expression of VEGF in HCC, which can increase the efficacy of IFN-α, providing a theoretical basis for clinical application.

• anti-inflammatory
• anticancer
• black ginseng
• steaming and drying
• transformed ginsenosides

• Drug Development
• Molecular Structure
• Panax/chemistry
• Panax/classification
• Saponins/chemistry
• Secondary Metabolism

• bioavailability
• delivery system
• ginsenosides
• permeability
• solubility

Ginseng has been traditionally used for several millennia in Asian countries, including Korea, China, and Japan, not only as a nourishing and tonifying agent but also as a therapeutic agent for a variety of diseases. In recent years, the various effects of red ginseng including immunity improvement, fatigue relief, memory improvement, blood circulation improvement, antioxidation, mitigation of menopausal women's symptoms, and anticancer an effect have been reported in clinical as well as basic research. Around the world, there is a trend of the rising consumption of health functional foods on the level of disease prevention along with increased interest in maintaining health because of population aging and the awareness of lifestyle diseases and chronic diseases. Red ginseng occupies an important position as a health functional food. But till now, international ginseng monographs including those of the World Health Organization have been based on data on white ginseng and have mentioned red ginseng only partly. Therefore, the red ginseng monograph is needed for component of red ginseng, functionality certified as a health functional food in the Korea Food and Drug Administration, major efficacy, action mechanism, and safety. The present red ginseng monograph will contribute to providing accurate information on red ginseng to agencies, businesses, and consumers both in South Korea and abroad.

• Health functional foods
• Red ginseng
• Red ginseng monograph

We have explored the effects of 20(S)-protopanaxadiol (aPPD), a naturally derived ginsenoside, against androgen receptor (AR) positive castration resistant prostate cancer (CRPC) xenograft tumors and have examined its interactions with AR. In silico docking studies for aPPD binding to AR, alongside transactivation bioassays and in vivo efficacy studies were carried out in the castration-resistant C4-2 xenograft model. Immunohistochemical (IHC) and Western blot analyses followed by evaluation of AR, apoptotic, cell cycle and proliferative markers in excised tumors was performed. The growth of established CRPC tumors was inhibited by 53% with aPPD and a corresponding decrease in serum PSA was seen compared to controls. The IHC data revealed that Ki-67 was significantly lower for aPPD treated tumors and was associated with elevated p21 and cleaved caspase-3 expression, compared to vehicle treatment. Furthermore, aPPD decreased AR protein expression in xenograft tumors, while significantly upregulating p27 and Bax protein levels. In vitro data supporting this suggests that aPPD binds to and significantly inhibits the N-terminal or the DNA binding domains of AR. The AR androgen binding site docking score for androgen (dihydrotestosterone) was −11.1, while that of aPPD was −7.1. The novel findings described herein indicate aPPD potently inhibits PCa in vivo partly via inhibition of a site on the AR N-terminal domain. This manifested as cell cycle arrest and concurrent induction of apoptosis via an increase in Bax, cleaved-caspase-3, p27 and p21 expression.

• 20(S)-protopanaxadiol ginsenoside
• androgen receptor
• apoptosis
• castration resistant prostate cancer

• Korean red ginseng
• paraventricular nucleus neurons
• patch-clamp techniques

• Animals
• Dose-Response Relationship, Drug
• Male
• Membrane Potentials/drug effects
• Mice
• Mice, Inbred ICR
• Panax
• Paraventricular Hypothalamic Nucleus/cytology
• Paraventricular Hypothalamic Nucleus/drug effects
• Patch-Clamp Techniques
• Plant Extracts/pharmacology
• Receptors, N-Methyl-D-Aspartate/drug effects
• Receptors, N-Methyl-D-Aspartate/metabolism

• National Research Foundation of Korea

Chemoresistance is a major clinical problem compromising the successful treatment of cancer. One exciting approach is the eradication of cancer stem/tumor-initiating cells (jointly CSCs), which account for tumor initiation, progression, and drug resistance. Here we show for the first time, with mechanism-based evidence, that ginsenoside-Rb1, a natural saponin isolated from the rhizome of Panax quinquefolius and notoginseng, exhibits potent cytotoxicity on CSCs. Rb1 and its metabolite compound K could effectively suppress CSC self-renewal without regrowth. Rb1 and compound K treatment also sensitized the CSCs to clinically relevant doses of cisplatin and paclitaxel. These effects were associated with the Wnt/β-catenin signaling pathway by downregulating β-catenin/T-cell factor-dependent transcription and expression of its target genes ATP-binding cassette G2 and P-glycoprotein. We also identified reversal of epithelial-to-mesenchymal transition as a new player in the Rb1 and compound K-mediated inhibition of CSCs. Rb1 and compound K treatment also inhibited the self-renewal of CSCs derived from ovarian carcinoma patients as well as in xenograft tumor model. Moreover, we did not observe toxicity in response to doses of Rb1 and compound K that produced an anti-CSC effect. Therefore, Rb1 should be explored further as a promising nutraceutical prototype of treating refractory tumors.

• Wnt/β-catenin signaling
• cancer stem cells
• chemoresistance
• ginsenoside
• ovarian cancer

Oxidative stress induces the production of reactive oxygen species (ROS), which play important causative roles in various pathological conditions. Black ginseng (BG), a type of steam-processed ginseng, has drawn significant attention due to its biological activity, and is more potent than white ginseng (WG) or red ginseng (RG).

We evaluated the protective effects of BG extract (BGE) against oxidative stress-induced cellular damage, in comparison with WG extract (WGE) and RG extract (RGE) in a cell culture model. Ethanolic extracts of WG, RG, and BG were used to evaluate ginsenoside profiles, total polyphenols, flavonoid contents, and antioxidant activity. Using AML-12 cells treated with H₂O₂, the protective effects of WGE, RGE, and BGE on cellular redox status, DNA, protein, lipid damage, and apoptosis levels were investigated.

BGE exhibited significantly enhanced antioxidant potential, as well as total flavonoid and polyphenol contents. ATP levels were significantly higher in BGE-treated cells than in control; ROS generation and glutathione disulfide levels were lower but glutathione (GSH) and NADPH levels were higher in BGE-treated cells than in other groups. Pretreatment with BGE inhibited apoptosis and therefore protected cells from oxidative stress-induced cellular damage, probably through ROS scavenging.

Collectively, our results demonstrate that BGE protects AML-12 cells from oxidative stress-induced cellular damages more effectively than WGE or RGE, through ROS scavenging, maintenance of redox status, and activation of the antioxidant defense system.

• Panax ginseng
• antioxidant
• black ginseng
• chemoprotection
• oxidative stress

• AMPK
• Anti-diabetic
• Black ginseng
• Glut

• 12-Chloracetyl-PPD
• 25-OH-PPD
• Apoptosis
• Cell cycle
• Reactive oxygen species

• Antineoplastic Agents, Phytogenic/chemistry
• Antineoplastic Agents, Phytogenic/pharmacology
• Apoptosis/drug effects
• Cell Line, Tumor
• Cell Proliferation/drug effects
• G2 Phase Cell Cycle Checkpoints/drug effects
• Humans
• M Phase Cell Cycle Checkpoints/drug effects
• Panax/chemistry
• Reactive Oxygen Species/metabolism
• Triterpenes/chemistry
• Triterpenes/pharmacology
• Dammaranes

• Korean Red Ginseng
• antitumorigenic activity
• nonsaponin fraction
• saponin fraction
• xenograft mouse model

AD-2 (20(R)-dammarane-3b, 12b, 20, 25-tetrol; 25-OH-PPD) is a ginsenoside and isolated from Panax ginseng, showing anticancer activity against extensive human cancer cell lines. In this study, effects and mechanisms of 1C ((20R)-3b-O-(L-alanyl)-dammarane-12b, 20, 25-triol), a modified version of AD-2, were evaluated for its development as a novel anticancer drug.

MTT assay was performed to evaluate cell cytotoxic activity. Cell cycle and levels of reactive oxygen species (ROS) were determined using flow cytometry analysis. Western blotting was employed to analyze signaling pathways.

1C concentration-dependently reduces prostate cancer cell viability without affecting normal human gastric epithelial cell line-1 viability. In LNCaP prostate cancer cells, 1C triggered apoptosis via Bcl-2 family-mediated mitochondria pathway, downregulated expression of mouse double minute 2, upregulated expression of p53 and stimulated ROS production. ROS scavenger, N-acetylcysteine, can attenuate 1C-induced apoptosis. 1C also inhibited the proliferation of LNCaP cells through inhibition on Wnt/β-catenin signaling pathway.

1C shows obvious anticancer activity based on inducing cell apoptosis by Bcl-2 family-mediated mitochondria pathway and ROS production, inhibiting Wnt/β-catenin signaling pathway. These findings demonstrate that 1C may provide leads as a potential agent for cancer therapy.

•

Ginseng saponin derivative 1C was obtained by structural modification.

• 1C
• AD-2
• Wnt/β-catenin pathway
• apoptosis
• reactive oxygen species

• Panax sp.
• ginseng
• hepatoprotective
• hepatotoxic

• Apoptosis
• Cell cycle arrest
• Chikusetsusaponin IVa methyl ester
• Metastasis
• Ovarian cancer
• Panacis Japonici Rhizoma

• Antineoplastic Agents, Phytogenic/chemistry
• Antineoplastic Agents, Phytogenic/pharmacology
• Apoptosis/drug effects
• Caspase 3/metabolism
• Cell Line, Tumor
• Cell Movement/drug effects
• Cell Proliferation/drug effects
• Cell Survival/drug effects
• Cyclin D1/metabolism
• Cyclin-Dependent Kinase 2/metabolism
• Drug Screening Assays, Antitumor
• Drugs, Chinese Herbal/chemistry
• Female
• G1 Phase Cell Cycle Checkpoints/drug effects
• Humans
• Membrane Potential, Mitochondrial/drug effects
• Molecular Structure
• Oleanolic Acid/analogs & derivatives
• Oleanolic Acid/chemistry
• Oleanolic Acid/pharmacology
• Ovarian Neoplasms/drug therapy
• Ovarian Neoplasms/metabolism
• Ovarian Neoplasms/pathology
• Saponins/chemistry
• Saponins/pharmacology

Recently, most anticancer drugs are derived from natural resources such as marine, microbial, and botanical sources, but the low success rates of chemotherapies and the development of multidrug resistance emphasize the importance of discovering new compounds that are both safe and effective against cancer. Ginseng types, including Asian ginseng, American ginseng, and notoginseng, have been used traditionally to treat various diseases, due to their immunomodulatory, neuroprotective, antioxidative, and antitumor activities. Accumulating reports have shown that ginsenosides, the major active component of ginseng, were helpful for tumor treatment. 20(S)-Protopanaxadiol (PDS) and 20(S)-protopanaxatriol saponins (PTS) are two characteristic types of triterpenoid saponins in ginsenosides. PTS holds capacity to interfere with crucial metabolism, while PDS could affect cell cycle distribution and prodeath signaling. This review aims at providing an overview of PTS and PDS, as well as their metabolites, regarding their different anticancer effects with the proposal that these compounds might be potent additions to the current chemotherapeutic strategy against cancer.

Colorectal cancer represents the third most common and the second deadliest type of cancer for both men and women in the United States claiming over 50000 lives in 2014. The 5-year survival rate for patients diagnosed with metastatic colon and rectal cancer is < 15%. Early detection and more effective treatments are urgently needed to reduce morbidity and mortality of patients afflicted with this disease. Here we will review the risk factors and current treatment paradigms for colorectal cancer, with an emphasis on the role of chemoprevention as they relate to epidermal growth factor receptor (EGFR) blockade. We will discuss how various EGFR ligands are upregulated in the presence of Western diets high in saturated and N-6 polyunsaturated fats. We will also outline the various mechanisms of EGFR inhibition that are induced by naturally occurring chemopreventative agents such as ginseng, green tea, and curcumin. Finally, we will discuss the current role of targeted chemotherapy in colon cancer and outline the limitations of our current treatment options, describing mechanisms of resistance and escape.

• Chemoprevention
• Colon cancer
• Epidermal growth factor receptor
• Western diet
• Curcumin
• Green tea
• Ginseng

• UL1 TR000430 NCATS NIH HHS

• Panax ginseng
• elasticity
• enzyme-treated red ginseng
• human skin
• wrinkle

Although the incidence of colorectal cancer (CRC) has been declining in recent decades, it remains a major public health issue as a leading cause of cancer mortality and morbidity worldwide. Prevention is one milestone for this disease. Extensive study has demonstrated that a diet containing fruits, vegetables, and spices has the potential to prevent CRC. The specific constituents in the dietary foods which are responsible for preventing CRC and the possible mechanisms have also been investigated extensively. Various phytochemicals have been identified in fruits, vegetables, and spices which exhibit chemopreventive potential. In this review article, chemopreventive effects of phytochemicals including curcumin, polysaccharides (apple polysaccharides and mushroom glucans), saponins (Paris saponins, ginsenosides and soy saponins), resveratrol, and quercetin on CRC and the mechanisms are discussed. This review proposes the need for more clinical evidence for the effects of phytochemicals against CRC in large trials. The conclusion of the review is that these phytochemicals might be therapeutic candidates in the campaign against CRC.

• Phytochemicals
• Fruits
• Vegetables
• Spices
• Colorectal cancer
• Cancer prevention

• Animals
• Anticarcinogenic Agents/therapeutic use
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/epidemiology
• Colorectal Neoplasms/prevention & control
• Diet/adverse effects
• Fruit
• Humans
• Phytochemicals/therapeutic use
• Risk Factors
• Risk Reduction Behavior
• Spices
• Vegetables

• Panax ginseng
• cachexia
• cisplatin
• rat
• sickness behaviors

• Korean red ginseng
• antioxidant.
• glutathione S-transferase placental form positive foci
• hepatocarcinogenesis
• rat

The number of CD34+ cells in a peripheral blood stem cell collection is the key factor in predicting successful treatment of hematologic malignancies. Korean Red Ginseng (KRG) (Panax ginseng C.A. Meyer) is the most popular medicinal herb in Korea. The objective of this study was to determine the effect of KRG on hematopoietic colony formation.

Bone marrow (BM) samples were obtained from 8 human donors after acquiring informed consent. BM mononuclear cells (MNCs) were isolated, and CD34+ cells were sorted using magnetic beads. The sorted CD34+ cells were incubated with or without total extract of KRG (50 µg/mL, 100 µg/mL) or Ginsenoside Rg1 (100 µg/mL), and the hematopoietic colony assay was performed using methylcellulose semisolid medium. The CD34+ cell counts were measured by a single platform assay using flow cytometry.

The numbers of human BM-MNCs and CD34+ cells obtained after purification were variable among donors (5.6×10⁷ and 1.3-48×10⁷ and 8.9×10⁴ and 1.8-80×10⁴, respectively). The cells expanded 1,944 times after incubation for 12 d. Total extract of KRG added to the hematopoietic stem cell (HSC)-specific medium increased CD34+ cell counts 3.6 times compared to 2.6 times when using HSC medium alone. Total numbers of hematopoietic colonies in KRG medium were more than those observed in conventional medium, especially that of erythroid colonies such as burst forming unit-erythroid.

Total extract of KRG facilitated CD34+ cell expansion and hematopoietic colony formation, especially of the erythroid lineage.

• CD34 antigen
• Ginseng
• Hematopoietic colony-forming unit
• Korea traditional medicine

Helicobacter pylori-induced gastric inflammation includes induction of inflammatory mediators interleukin (IL)-8 and inducible nitric oxide synthase (iNOS), which are mediated by oxidant-sensitive transcription factor NF-κB. High levels of lipid peroxide (LPO) and increased activity of myeloperoxidase (MPO), a biomarker of neutrophil infiltration, are observed in H. pylori-infected gastric mucosa. Panax ginseng Meyer, a Korean herb medicine, is widely used in Asian countries for its biological activities including anti-inflammatory efficacy. The present study aims to investigate whether Korean Red Ginseng extract (RGE) inhibits H. pylori-induced gastric inflammation in Mongolian gerbils. One wk after intragastric inoculation with H. pylori, Mongolian gerbils were fed with either the control diet or the diet containing RGE (200 mg RGE/gerbil) for 6 wk. The following were determined in gastric mucosa: the number of viable H. pylori in stomach; MPO activity; LPO level; mRNA and protein levels of keratinocyte chemoattractant factor (KC, a rodent IL-8 homolog), IL-1β, and iNOS; protein level of phospho-IκBα (which reflects the activation of NF-κB); and histology. As a result, RGE suppressed H. pylori-induced mRNA and protein levels of KC, IL-1β, and iNOS in gastric mucosa. RGE also inhibited H. pylori-induced phosphorylation of IκBα and increases in LPO level and MPO activity of gastric mucosa. RGE did not affect viable H. pylori colonization in the stomach, but improved the histological grade of infiltration of polymorphonuclear neutrophils, intestinal metaplasia, and hyperplasia. In conclusion, RGE inhibits H. pylori-induced gastric inflammation by suppressing induction of inflammatory mediators (KC, IL-1β, iNOS), MPO activity, and LPO level in H. pylori-infected gastric mucosa.

• Helicobacter pylori
• Korean Red Ginseng extract
• Mongolian gerbil
• gastric inflammation

Serum and liver metabolites in rats fed red ginseng (RG) were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. The mass data were analyzed by partial least squares-discriminant analysis (PLS-DA) to discriminate between control and RG groups and identify metabolites contributing to this discrimination. The RG group was clearly separated from the control group on PLS-DA scores plot for serum samples, but not liver samples. The major metabolites contributing to the discrimination included lipid metabolites (lysophosphatidylcholine, acyl-carnitine, and sphingosine), isoleucine, nicotinamide, and corticosterone in the serum; the blood levels of all but isoleucine were reduced by RG administration. Not all metabolites were positively correlated with the health benefits of RG. However, the blood levels of lysophosphatidylcholine, which stimulate various diseases, and long-chain acylcarnitines and corticosterone, which activate the stress response, were reduced by RG, suggesting long-term RG might relieve stress and prevent physiological and biological problems.

• Corticoterone
• Lysophosphatidylcholines
• Metabolomics
• Red ginseng
• Ultra-performance liquid chromatographyquadrupole time-of-flight mass spectrometry

• Cyclooxygenase-2
• Heme oxygenase-1
• Ionizing radiation
• Red ginseng

Endothelial barrier integrity is essential for vascular homeostasis and increased vascular permeability and has been implicated in many pathological processes, including diabetic retinopathy. Here, we investigated the effect of Rk1, a ginsenoside extracted from sun ginseng, on regulation of endothelial barrier function. In human retinal endothelial cells, Rk1 strongly inhibited permeability induced by VEGF, advanced glycation end-product, thrombin, or histamine. Furthermore, Rk1 significantly reduced the vessel leakiness of retina in a diabetic mouse model. This anti-permeability activity of Rk1 is correlated with enhanced stability and positioning of tight junction proteins at the boundary between cells. Signaling experiments revealed that Rk1 induces phosphorylation of myosin light chain and cortactin, which are critical regulators for the formation of the cortical actin ring structure and endothelial barrier. These findings raise the possibility that ginsenoside Rk1 could be exploited as a novel prototype compound for the prevention of human diseases that are characterized by vascular leakage.

• Actins/chemistry
• Actins/metabolism
• Animals
• Blood Vessels/cytology
• Blood Vessels/drug effects
• Blood Vessels/metabolism
• Cortactin/metabolism
• Endothelial Cells/drug effects
• Endothelial Cells/metabolism
• Ginsenosides/pharmacology
• Glycation End Products, Advanced/pharmacology
• Histamine/pharmacology
• Humans
• Male
• Mice
• Myosin Light Chains/metabolism
• Permeability/drug effects
• Phosphorylation/drug effects
• Retina/cytology
• Thrombin/pharmacology
• Tight Junctions/drug effects
• Tight Junctions/metabolism
• Vascular Endothelial Growth Factor A/pharmacology