Anti-inflammatory Activity of Prosapogenin Methyl Ester of Platycodin D via Nuclear Factor-kappaB Pathway Inhibition

Abstract

Immune responses to infection or to localized injury or trauma are among the main causes of local or systemic inflammation. Despite the beneficial effect of inflammation in limiting responses to cellular and organ damage, a breakdown in the regulation of the inflammatory response may result in a wide range of chronic diseases such as arthritis, inflammatory bowel diseases, asthma and others. 1)Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, sulindac and indomethacin, are widely believed to have anti-inflammatory effects due to their ability to inhibit prostanoid production, and relieve inflammation by inhibiting cyclooxygenase (COX).COX are the rate-limiting enzymes that catalyze the formation of prostaglandins from arachidonic acid.2-5) Levels of prostaglandins increase early in the course of the inflammatory process. The constitutive isoform, COX-1, is expressed in most tissues predominantly in platelets, gastrointestinal tract, kidney, and liver.2-4) The inducible isoform, COX-2, is activated in response to pro-inflammatory cytokines and growth factors.3,4) Because COX-2 protein is induced by several kinds of stimuli in inflammatory cells, inhibitors of COX-2 protein induction might be candidates for the new-type NSAIDs. Also, inflammation is associated with inducible nitric oxide synthase (iNOS). Especially, nitric oxide (NO) produced by activated macrophages via iNOS was initially considered a component of innate immunity in the fight against infections. 6) It has been well accepted that nuclear-factor-kB (NF-kB) signaling pathway plays important roles in the inflammation, control of cell growth, apoptosis, stress response, and many other physiological processes. [7][8][9][10][11] There are several important molecules such as NF-kB, inhibitor kB (IkB), IKK, within NF-kB signaling pathway.12) NF-kB is a key protein in the pathway, and has been described as a major culprit and a therapeutic target in inflammation and cancer. [13][14][15][16] It is activated by lipopolysaccharide (LPS), which is a mammalian transcription factor that controls various genes that are important for immunity and inflammation.17) NF-kB is mainly composed of p50 and p65. 17) In unstimulated cells, NF-kB is present in the cytoplasm through interactions with an inhibitory protein, IkB. NF-kB is activated by IkBa degradation following phosphorylation of IkBa. 18)Platycodi Radix is the root of Platycodon grandiflorum A. DE (Campanulaceae).19) It is edible and the principal herb in Oriental medicine for diseases of the lungs and throat, and is commonly used for the inflammatory conditions of the eyes, ears, and sinuses.19) Saponins (PS) are the primary constituents of Platycodi Radix, [20][21][22] and they are responsible for diverse effects including anti-inflammation, [23][24][25][26] anti-allergy, 23) anti-tumor, 27) augmentation of immune response, [28][29][30] and stimulating the apoptosis in skin cells. 27) In the last decade, PS has generated renewed interests due to their pharmacological potentials for healing the...

Platycodin D exerts anti-tumor efficacy in H22 tumor-bearing mice via improving immune function and inducing apoptosis

“…Platycodin D (PD, Fig. 1), the major active constituent of P. grandiflorum, has received more and more attention due to its pharmaceutical effects, including anti-inflammation (Chung et al, 2008;Zhang et al, 2015), anti-obesity (Zhao et al, 2006), anti-atherosclerosis (Wu et al, 2012), hepatoprotective Li et al, 2015a), and anti-tumor (Luan et al, 2014;Zhao et al, 2015) effects. It is worth mentioning that PD exerts remarkable anti-cancer effects on different kinds of cancer cell lines, including HepG2, MDA-MB-231, U937, K562, PC3, and MCF-7, with main molecular mechanisms such as promoting apoptosis and inhibiting migration and invasion (Tang et al, 2014;Li et al, 2014;Yu and Kim, 2010;Shin et al, 2009;Kim et al, 2008).…”

Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene

“…Platycodin D (PD), a triterpenoid saponin derived from the roots of Platycodin grandiflorum, has been reported to possess a wide rangeof health benefits, such as anti-atherosclerotic (4), anti-inflammatory (5,6), hypocholesterolemic, and anti-obesity effects (7), as well as spermicidal and contraceptive activity (8). Among the various health benefits of PD, anticancer effects have been noted in several cancer cell lines, including lung cancer cells (9), hepatocellular carcinoma cells (10), gastric cancer cells (11), prostate cancer cells (12), and leukemia cells (13,14).…”

Platycodin D Blocks Breast Cancer-Induced Bone Destruction by Inhibiting Osteoclastogenesis and the Growth of Breast Cancer Cells

“…Platycodin D is a bioactive triterpenoid saponin that is isolated from the root of Platycodon grandiflorum (Companulaceae) and possesses various pharmacological activities, including anti-cancer, anti-angiogenic, anti-inflammatory, and anti-obesity effects [10,11,12,13,14]. In particular, many studies have reported the anti-cancer effects of platycodin D in breast cancer cells.…”