Anti-stress Effects of 20(<i>S</i>)-Protopanaxadiol and 20(<i>S</i>)-Protopanaxatriol in Immobilized Mice

Abstract

Stress is a common and unavoidable phenomenon in human life.1,2) Exposure to stress induces glucocorticoid release via the activation of the hypothalamo-pituitary-adrenal (HPA) axis and it modulates immune cells and further modulates cytokine production.3-5) Among these cytokines, proinflammatory interleukin (IL)-6 and tumor necrosis factor (TNF)-α are up-regulated by stress and are associated with host defense systems.6) The failure to cope with stress exacerbates both psychological and immune disorders, including anxiety, depression, cardiovascular disturbances, neuronal degeneration of the central nervous system and chronic fatigue syndromes. 7,8) Ginseng (the root of Panax ginseng C.A. MEYER, Araliaceae) has been widely used as a traditional Chinese medicine for the treatment of various maladies such as inflammation, anxiety, depression, fatigue, and stress. Its representative constituents are dammarane-type ginsenosides, which are classified into protopanaxadiols, such as ginsenosides Rb1, Rb2, Rc, and Rd, and protopanaxatriols such as ginsenosides Re and Rg1.9,10) These ginsenosides have been previously reported to show various biological activities, including anti-inflammatory, 10,11) anti-allergic, 12) anxiolytic, 13) anti-stress 14) and anti-tumor activities. 16-19) These metabolites have many pharmacological activities similar to ginseng, including anti-tumor, anti-diabetic, and anti-inflammatory effects.20-22) Therefore, to understand the pharmacological effect of ginseng, understanding the biological activities of two metabolites, 20(S)-protopanaxadiol and 20(S)-protopanaxatriol, of various ginsenosides is important. Nevertheless, the pharmacological effects of the ginsenoside metabolites have not been studied thoroughly.In our preliminary study, we also found that ginseng saponin extract showed anti-stress effect in mice. Therefore, in the present study, we investigated further the anti-stress effects of ginseng saponin metabolites, 20(S)-protopanaxadiol (PPD) and 20(S)-protopanaxatriol (PPT), in immobilized mice. MATERIALS AND METHODSMaterials Bicuculline, buspirone, dexamethasone, flumazenil and WAY-100635 were purchased from Sigma (St. Louis, MO, U.S.A.). 20(S)-Protopanaxadiol (purity ≥98% by HPLC) and 20(S)-protopanaxatriol (purity ≥98% by HPLC) were purchased from Ambo Institute (Daejeon, Korea). Orally administered 20(S)-protopanaxadiol and 20(S)-protopanaxatriol were suspended in 0.5% carboxymethylcellulose (CMC) solution and intraperitoneally injected buspirone, flumazenil, bicuculline, and WAY-100635 were dissolved in sterilized saline.Animals Male ICR mice (age, 7 weeks-old; weight, 24-28 g) were purchased from Samtako Biokorea (Seoul, Korea) and acclimated for 1 week before use. All animals were maintained under a constant temperature (24±2°C) and humidity (60±10%) with an alternating 12 h light-dark cycle. They were fed standard laboratory chow (Samyang Co., Seoul, Korea) with tap water ad libitum. Each group consisted of 7 mice for all experiments. The mice were randomly divided

Neuroprotective Effects of Dammarane-Type Saponins from Panax notoginseng on Glutamate-Induced Cell Damage in PC12 Cells

“…Compound 4 is an effective compound, and earlier researches have confirmed that it had significant effects, including cardioprotective [21] and antiobesity bioactivities [22]. In recent years, neuroprotective effects of compound 4 were also reported [23,24]. However, this study was the first to evaluate its effects on NDs in an in vitro experimental model.…”

Metabolite profiling of ginsenosides in rat plasma, urine and feces by LC–MS/MS and its application to a pharmacokinetic study after oral administration of Panax ginseng extract

“…Qiang et al reported that, after oral administration, Rb1, Rc, Rb2, Rb3 are mainly metabolized to compound K via Rd by gut microbiota (Qiang et al, ). Orally administered ginsenoside Rb1 and Re are metabolized to compound K via ginsenoside Rd and PPT and Rh1 via Rg1 by gut microbiota (Oh, Kim, Choi, Kim, & Kim, ). Wang et al reported that Rg1 and Re are converted to Rh1 and F1 by gut microbiota.…”

Panax Notoginseng Saponins: A Review of Its Mechanisms of Antidepressant or Anxiolytic Effects and Network Analysis on Phytochemistry and Pharmacology

“…PNS (58.6%) significantly decreased immobility time in the forced swim test with little effect on locomotion in the chronic mild stress model, and significantly improved the level of animal activity and sucrose consumption [67], which may have antidepressant-like effects [45,53,64,65],. Besides, when PNS was digested by Snail Enzyme to 50%, it produced the best antidepressant effects, and the main active ingredient is ginsenosides Rb1, Rb2, Rc and Rb3 [60,[68][69][70][71]. These were shown in table 1.…”

“…Recent studies have found that Panax notoginseng saponins (PNS) have good preventive and therapeutic effects on neurological diseases of the brain [28], especially in antidepressant [26][27][28] and anti-anxiety effects [25,28,40]. The preliminary determination was that anti-depressant and anti-anxiety effects may occur by increasing the levels of the brain monoamine neurotransmitters 5-hydroxytryptamine (5-HT) [41,42] and norepinephrine (NE) in the central nervous system.…”