Disease relevance of Protopanaxadiol

• We previously screened neurite outgrowth activities of several Ginseng drugs in human neuroblastoma, and demonstrated that protopanaxadiol (ppd)-type saponins were active constituents [1].
• IH-901 [20-O-beta-d-glucopyranosyl-20(S)-protopanaxadiol], an intestinal bacterial metabolite derived from protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess antitumor effects, including inhibition of invasion, metastasis and angiogenesis and induction of tumor cell apoptosis [2].
• AG extract, fermented AG extract and protopanaxadiol potently inhibited the growth of Helicobacter pylori [3].
• When we compared the effects of protopanaxadiol (PD) ginsenosides and protopanaxatriol (PT) ginsenosides against CRD-acetic acid-induced visceral hypersensitivity, we found that PT but not PD ginsenosides significantly attenuated the CRD-acetic acid-induced visceral hypersensitivity [4].

Psychiatry related information on Protopanaxadiol

• We previously showed that 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (M1), a metabolite of protopanaxadiol-type ginseng saponins by intestinal bacteria had axonal extension activity in degenerated neurons, and improved memory disorder and synaptic loss induced by an active fragment of amyloid beta, Abeta(25-35) [5].
• Korean red ginseng saponins with low ratios of protopanaxadiol and protopanaxatriol saponin improve scopolamine-induced learning disability and spatial working memory in mice [6].

High impact information on Protopanaxadiol

• Recently, a novel intestinal bacterial metabolite of ginseng protopanaxadiol saponins, i.e., 20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol (IH-901), has been reported to induce apoptosis in a variety of cancer cells [7].
• M1, M2, M3, M5, and M12 are protopanaxadiol saponin-derived metabolites [8].
• Therefore, these results imply that the protopanaxadiol saponins are prodrugs, and they show more potent inhibitory activity following metabolism in the digestive tract [8].
• Adjuvant effects of protopanaxadiol and protopanaxatriol saponins from ginseng roots on the immune responses to ovalbumin in mice [9].
• The structure-activity relationship studies suggested that the length of sugar side chains at position C-20 and the linkage of glucose moiety at position C-3 of protopanaxadiol could affect the haemolytic and adjuvant activities of PDS [10].

Biological context of Protopanaxadiol

• 20(S)- and delta20-ginsenosides Rg3, protopanaxadiol-type saponins, were found to be relatively potent PAF antagonists (IC50 = 4.9 x 10(-5) M and 9.2 x 10(-5) M, respectively) [11].
• Ginsenoside C (protopanaxadiol group ginseng saponin) showed a significantly longer half-life, higher plasma protein binding, and lower metabolic and renal clearance than ginsenosides A1, A2, and B2 (protopanaxatriol group ginseng saponins) [12].

Anatomical context of Protopanaxadiol

• In the current study, we have investigated the antitumor effect of a novel ginseng protopanaxadiol saponin bacterial metabolic derivative, 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol (IH-901), in eight human myeloma cell lines [13].
• Mechanistic studies on protopanaxadiol, Rh2, and ginseng (Panax quinquefolius) extract induced cytotoxicity in intestinal Caco-2 cells [14].
• These findings demonstrate that ginsenosides from the protopanaxatriol group but not from the protopanaxadiol group enhance the release of nitric oxide from endothelial cells and may contribute to the beneficial effect of ginseng on the cardiovascular system [15].
• On the other hand, in mouse vas deferens (MVD), the contractions were increased by PT and PD, however, GTS was almost without effect [16].
• Acid-treated ginseng (AG) extract, fermented AG extract, ginsenoside Rh2 and protopanaxadiol showed potent cytotoxicity against tumor cell lines [3].

Associations of Protopanaxadiol with other chemical compounds

• Cell-cycle analysis confirmed apoptosis with PD and PT treatment of THP-1 cells resulting in a buildup of sub-G1 cells after 24, 48, and 72 h of treatment [17].
• Uptake and metabolism of ginsenoside Rh2 and its aglycon protopanaxadiol by Caco-2 cells [18].

Gene context of Protopanaxadiol

• In vitro inhibitory effect of protopanaxadiol ginsenosides on tumor necrosis factor (TNF)-alpha production and its modulation by known TNF-alpha antagonists [19].
• The present study demonstrated in vivo and in vitro antimetastatic activities of a major intestinal bacterial metabolite M1 formed from protopanaxadiol saponins of ginseng (the root of Panax ginseng C. A. Meyer) in comparison with its whole standardized extract and ginsenosides Rb1, Rb2, and Rc [20].
• A carrier protein (bovine serum albumin (BSA)) was coupled to the C-26 position on the unsaturated side chain of the protopanaxadiol moiety to prepare the immunogen [21].
• However, protopanaxadiol glycoside ginsenosides Rb1, Rb2 and Rc isolated from ginseng were mostly not transformed to ginsenoside Rg3 by the incubation in neutral condition [3].
• Ginseng total saponins and one of the constituents, protopanaxatriol saponin, suppressed the development of morphine tolerance in a concentration dependent manner in GPI preparation, though another constituent, protopanaxadiol saponin, did not affect the tolerance development substantially [22].

Analytical, diagnostic and therapeutic context of Protopanaxadiol

• The novel intestinal bacterial metabolites of ginseng protopanaxadiol saponins have recently been found and isolated after the oral administration of ginseng extract in human and rats [23].
• Enzyme immunoassay (EIA) of ginsenoside Rb1 (GRb1), one of the glucosides of protopanaxadiol from Panax ginseng, was explored [21].
• Protopanaxadiol ginsenosides Rb2 and Rc were transformed using cell-free extracts from various edible food microorganisms and then analyzed by TLC and HPLC [24].
• The newly established double staining with the Western blotting methods was applied for the determination of ginsenosides possessing protopanaxadiol or protopanaxatriol and the number of sugar depending on the stained color and their Rf values in the Panax plants [25].

References