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Panax ginseng induces human Type I collagen synthesis through activation of Smad signaling.

Skin aging appears to be principally related to a decrease in levels of Type I collagen, the primary component of the dermal layer of skin. It is important to introduce an efficient agent for effective management of skin aging; this agent should have the fewest possible side effects and the greatest wrinkle-reducing effect. In the course of screening collagen production-promoting agents, we obtained Panax ginseng C.A. Meyer. This study was designed to investigate the possible collagen production-promoting activities of Panax ginseng C.A. Meyer root extract (PGRE) in human dermal fibroblast cells. As a first step to this end, human COL1A2 promoter luciferase assay was performed in human dermal fibroblast cells. In this assay, PGRE activated human COL1A2 promoter activity in a concentration-dependent manner. Human Type I procollagen synthesis was also induced by PGRE. These results suggest that PGRE promotes collagen production in human dermal fibroblast cells. Additionally, we have attempted to characterize the mechanism of action of PGRE in Type I procollagen synthesis. PGRE was found to induce the phosphorylation of Smad2, an important transcription factor in the production of Type I procollagen. When applied topically in a human skin primary irritation test, PGRE did not induce any adverse reactions. Therefore, based on these results, we suggest the possibility that PGRE may be considered as an attractive, wrinkle-reducing candidate for topical application.

Antioxidants↗

Analysis of dencichine in Panax notoginseng by gas chromatography-mass spectrometry with ethyl chloroformate derivatization.

Dencichine (beta-N-oxalyl-l-alpha,beta-diaminopropionic acid) is a haemostatic agent present in well-known traditional Chinese medicinal herbs such as Panax notoginseng, as well as other Panax species. It is also a reported neurotoxic agent found in Lathyrus sativus (grass pea seed) and cycad seeds. A method was developed for quantitative determination of the non-protein amino acid, dencichine, in plant samples of P. notoginseng and the adventitious roots directly from the explants of P. notoginseng after derivatization with ethyl chloroformate (ECF) by gas chromatography-mass spectrometry (GC-MS). l-2-chlorophenylalanine was used as an internal standard. Calibration curves were linear (r(2)=0.9988, n=6) in the range of 10-800 microg/ml for dencichine. Limit of detection and quantification for dencichine were 0.5 microg/ml and 2 microg/ml, respectively. This rapid and specific method may be applied to the quantification of dencichine in complex medicinal plants and their products.

Amino Acids↗

Improved cognitive performance in human volunteers following administration of guarana (Paullinia cupana) extract: comparison and interaction with Panax ginseng.

Extracts from the plant guarana (Paullinia cupana) feature as putatively stimulating ingredients in a number of foods, drinks and dietary/herbal supplements. To date, little research in humans has examined the potential psychoactive effects of these extracts. Extracts of Panax ginseng, which are often sold in combination with guarana, contain similar potentially active components, and have been shown to modulate cognitive performance. In this double-blind, counterbalanced, placebo-controlled study, the cognitive and mood effects of separate single doses of: 75 mg of a dried ethanolic extract of guarana (approx 12% caffeine), 200 mg of Panax ginseng (G115), and their combination (75 mg/200 mg), were assessed in 28 healthy young (18-24) participants. On each day of the study (separated by a 7-day washout), cognitive performance and subjective mood were assessed pre-dose and at 1, 2.5, 4 and 6 h post-dose using the Cognitive Drug Research computerised assessment battery, Serial subtraction tasks and Bond-Lader mood scales. In comparison to placebo, all three treatments resulted in improved task performance throughout the day. In the case of guarana, improvements were seen across 'attention' tasks (but with some evidence of reduced accuracy), and on a sentence verification task. While also increasing the speed of attention task performance, both ginseng and the ginseng/guarana combination also enhanced the speed of memory task performance, with little evidence of modulated accuracy. Guarana and the combination, and to a lesser extent ginseng, also led to significant improvements in serial subtraction task performance. These results provide the first demonstration in humans of the psychoactive effects of guarana, and confirmation of the psychoactive properties of ginseng. Given the low caffeine content (9 mg) of this dose of guarana extract, the effects are unlikely to be attributable to its caffeine content.

Adult↗

Effect of American ginseng (Panax quinquefolium) on male copulatory behavior in the rat.

The effects of American ginseng (Panax quinquefolium) on male rat copulatory behavior were investigated. Adult Sprague-Dawley rats were administered either 10, 50 or 100 mg/kg of Panax quinquefolium or a sesame oil vehicle per os (p.o.) for 28 days and copulatory behavior parameters were measured. Ginseng-treated male rats demonstrated a significant decrease in mount, intromission and ejaculation latencies compared to vehicle controls. Hormone analyses revealed no difference in plasma luteinizing hormone or testosterone levels between ginseng- and vehicle-treated animals; however, plasma prolactin levels were significantly reduced by all doses of ginseng tested. When male rats were treated with the 100 mg/kg dose of ginseng for 1, 14 or 28 days, mount and intromission latencies were significantly reduced at 14 and 28 days of daily ginseng treatment, whereas ejaculation latency was significantly reduced after 1 day of ginseng treatment when compared to vehicle controls. Plasma prolactin levels were also significantly decreased after 14 and 28 days of daily ginseng administration. There were no differences in body weight or in testes, seminal vesicle, anterior pituitary or spleen weights between ginseng- and vehicle-treated rats. These results demonstrate that P. quinquefolium significantly facilitates male copulatory behavior. The reduction in plasma prolactin levels suggests that ginseng-induced alterations in dopaminergic neurotransmission may play a role in the ability of P. quinquefolium to stimulate copulatory behavior in the male rat.

Animals↗

Cancer chemopreventive activity of majonoside-R2 from Vietnamese ginseng, Panax vietnamensis.

In the course of our continuing search for novel cancer chemopreventive agents from natural sources, several kinds of Panax plants were screened. Consequently, the ocotillol-type saponin, majonoside-R2 (MR2), was obtained from the rhizome and root of Panax vietnamensis (Vietnamese ginseng) as an active constituent. MR2 exhibited potent anti-tumor-promoting activity on two-stage carcinogenesis test of mouse hepatic tumor using N-nitrosodiethylamine (DEN) as an initiator and phenobarbital (PB) as a promoter. Further, MR2 exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin induced by nitric oxide (NO) donor/12-O-tetradecanoylphorbol-13-acetate (TPA) or peroxynitrite/TPA.

Alkylating Agents↗

Effects of administration of the standardized Panax ginseng extract G115 on hepatic antioxidant function after exhaustive exercise.

The effect of prolonged treatment with the standardized Panax ginseng extract G115 on the antioxidant capacity of the liver was investigated. For this purpose, rats that had received G115 orally at different doses for 3 months and untreated control rats were subjected to exhaustive exercise on a treadmill. A bell-shaped dose response on running time was obtained. The results showed that the administration of G115 significantly increases the hepatic glutathione peroxidase activity (GPX) and the reduced glutathione (GSH) levels in the liver, with a dose-dependent reduction of the thiobarbituric acid reactant substances (TBARS). After the exercise, there is reduced hepatic lipid peroxidation, as evidenced by the TBARS levels in both the controls and the treated animals. The GPX (glutathione peroxidase) and SOD (superoxide dismutase) activity are also significantly increased in the groups receiving G115, compared with the controls. The hepatic transaminase levels, ALT (Alanine-amino-transferase) and AST (Aspartate-amino-transferase), in the recuperation phase 48 h after the exercise, indicate a clear hepatoprotective effect related to the administration of the standardized Panax ginseng extract G115. At hepatic level, G115 increases the antioxidant capacity, with a marked reduction of the effects of the oxidative stress induced by the exhaustive exercise.

Animals↗

Studies on the interaction of total saponins of panax notoginseng and human serum albumin by Fourier transform infrared spectroscopy.

Total saponins of panax notoginseng (TPNS), isolated from the roots of panax notoginseng (Burk) F.H. Chen, have been considered as the main active components of San-Chi and have various therapeutical actions. Their interactions with human serum albumin have been investigated by Fourier transformed infrared spectrometry and fluorescence methods. The results showed that TPNS combined with HSA through C=O and C-N groups of polypeptide chain. The drug-protein combination caused the significant loss of alpha-helix structure and the microenvironment changes of the tyrosine residues in protein at higher drug concentration. Combining the curve-fitting results of amide I and amide III bands, the alterations of protein secondary structure after drug complexation were quantitatively determined. The alpha-helix structure has a decrease of approximately 6%, from 55 to 49% and the beta-sheet increased approximately 3%, from 23 to 26% at high drug concentration. However, no major alterations were observed for the beta-turn and random coil structures up on drug-protein binding.

Chromatography, High Pressure Liquid↗

Structures of new dammarane-type Triterpene Saponins from the flower buds of Panax notoginseng and hepatoprotective effects of principal Ginseng Saponins.

The saponin fraction from the flower buds of Panax notoginseng exhibited protective effect on liver injury induced by d-galactosamine and lipopolysaccharide. From the saponin fraction with hepatoprotective effect, five new dammarane-type triterpene saponins, notoginsenosides-O (1), -P (2), -Q (3), -S (4), and -T (5), were isolated together with nine known protopanaxadiol oligoglycosides. The structures of the new saponins were elucidated on the basis of chemical and physicochemical evidence. The principal dammarane-type triterpene saponins from the roots and flower buds of Panax notoginseng were found to show potent hepatoprotective effects.

Animals↗

The effects of Panax ginseng on quality of life.

Panax ginseng is marketed and used to maintain natural energy, increase mental and physical abilities, improve mood and promote general health and well-being. Panax ginseng has been studied in a number of randomized clinical trials investigating its effect on physical and psychomotor performance, cognitive function, immunomodulation, diabetes mellitus and herpes simplex type-II infections. Equivocal results have been demonstrated for many of these indications. P. ginseng is also commonly used to promote quality of life (QoL). As a result, ginseng's effect on QoL has become an increasingly important endpoint in clinical trials. We reviewed all studies (n = 9) that determined the effect of P. ginseng on QoL. P. ginseng's has been evaluated at dosages of 80-400 mg. Study duration has spanned from 2 to 9 months. Several QoL measures have been used, ranging from widely accepted core instruments to unpublished investigator-derived questionnaires. In addition, many of the investigators utilized ginseng extracts that were supplemented with vitamins and minerals while others used only standardized ginseng extract. Populations evaluated also differed in terms of underlying morbidity. Nearly every study evaluated (n = 8) demonstrated some degree of QoL improvement. Beneficial effects were evident within instrument summary component scores but improvement in overall composite scores of QoL was rarely seen. However, findings were equivocal. While populations evaluated varied in terms of underlying morbidity, there did not appear to be a substantial difference in their response to ginseng with respect to QoL. Despite some positive results, improvement in overall health-related quality of life cannot, given the current research, be attributed to P. ginseng. However, the possibility that various facets of QoL may have improved and the potential of early transient effects cannot be discounted.

Adjuvants, Immunologic↗

Anti-septicaemic effect of polysaccharide from Panax ginseng by macrophage activation.

The aim of the present research was conducted to elucidate anti-septicaemic effect of a polysaccharide (PS) isolated from Panax ginseng C.A. Meyer (Araliaceae) by nitric oxide production from stimulated macrophage. In vitro assays for the activity measurement of PS, NO production test with Greiss reagent, phagocytic activity test using zymosan and cytokines production test using ELISA kit were also conducted. In vivo anti-septicaemic activity was assessed by using C57BL/6J mice. This was done with Staphylococcus aureus infection test. PS used at 0.025 mg/kg concentration showed a potent anti-septicaemic activity (80%, survival). However, it did not directly inhibit S. aureus in a minimum inhibitory concentration (MIC) test, conducted in vitro (data not shown). Nitric oxide production via macrophage activation showed the highest value of 5.5 nmol/ml at 1 microg/ml PS. In in vitro phagocytic activity test, PS at 10 microg/ml concentration showed a potent phagocytic activity for zymosan with 167% of the control. Production of TNF-alpha by macrophage activation at 10 microg/ml of PS was 96% lysis of L929. Also production of IL-1 and IL-6 by stimulation of macrophage with 100 microg/ml PS dose increased to 235 pg/ml and 0.47 ng/ml, respectively. The low mortality of PS treated (0.025 mg/kg) infected mice was concurrent with decreased bacterial content in the blood. Nitric oxide production in S. aureus infected mice whose macrophage was stimulated by PS (0.025 mg/kg) increased approximately 4 times than the untreated S. aureus infected group at 24 and 48 h incubation. In the PS treated (0.025 mg/kg) group, the intracellular concentration of S. aureus in macrophages decreased approximately by 50%, compared with the untreated group. Combine treatment with PS (0.025 mg/kg body weight) and vancomycin (10 mg/kg B.W.) resulted in 100% survival of the animals, whereas only 67% or 50% of the animals survived, respectively, when treated with PS or vancomycin alone. These results suggest that PS from Panax ginseng possess a potent anti-septicaemic activity by stimulating macrophage and a potentiality as an immunomodulator against sepsis occurred by Staphylococcus aureus.

Animals↗

Phylogenetic analysis based on 18S rRNA gene and matK gene sequences of Panax vietnamensis and five related species.

Panax vietnamensis was discovered recently in Vietnam. Its bamboo-like rhizomes, called Vietnamese Ginseng, have attracted considerable attention because of their specific pharmacological activities. In order to define the taxonomic position of this new species and include it in the molecular authentication of Ginseng drugs, the 18S ribosomal RNA gene and matK gene sequences of P. vietnamensis were determined and compared with those of its related taxa, P. japonicus var. major and P. pseudo-ginseng subsp. himalaicus, besides previously reported P. ginseng, P. japonicus and P. quinquefolius. The 18S rRNA gene sequences were found to be 1809 bps in length. The sequence of P. vietnamensis was identical to that of P. quinquefolius, and presented one base substitution from those of both P. japonicus var. major and P. pseudo-ginseng subsp. himalaicus. The matK gene sequences of 6 taxa were found to be 1509 bps in length. The sequence of P. vietnamensis differed from those of P. japonicus var. major, P. pseudo-ginseng subsp. himalaicus, P. ginseng, P. japonicus and P. quinquefolius at 4, 5, 9, 9 and 10 nucleotide positions, respectively. The phylogenetic tree reconstructed by the combined 18S rRNA-matK gene analysis using the maximum parsimony method showed that P. vietnamensis was sympatric with other Panax species and had a close relationship with P. japonicus var. major and P. pseudo-ginseng subsp. himalaicus.

Amino Acid Sequence↗

Application of sequence characterized amplified region (SCAR) analysis to authenticate Panax species and their adulterants.

A 420-bp RAPD fragment from Panax quinquefolius was converted to a sequence characterized amplified region (SCAR) marker. The main difference between the SCAR of P. quinquefolius and its homolog in P. ginseng is the presence of a 25 bp insertion in the latter. Primers derived from this sequence were successfully used to authenticate six Panax species and two common adulterants.

Base Sequence↗

Authentication of Panax species and their adulterants by random-primed polymerase chain reaction.

DNA from dried or fresh roots of three medicinal Panax species and their adulterants were amplified by AP-PCR or RAPD. Fingerprints for P. ginseng or P. quinquefolius were found to be consistent irrespective of plant source or age. On the other hand, very different fingerprints were obtained from adulterants. Hence the PCR approach may be used as a means to authenticate the concerned Panax species. Analysis of the degree of similarity of the fingerprints confirmed that P. ginseng is more closely related to P. quinquefolius than to P. notoginseng.

Base Sequence↗

Memory effects of standardized extracts of Panax ginseng (G115), Ginkgo biloba (GK 501) and their combination Gincosan (PHL-00701).

In experiments on young (aged 3 months) and old (aged 26 months) rats, using some conditioned-reflex methods with punishment or positive reinforcement for active and passive avoidance (shuttle-box, step-down, step-through, and water maze), we studied the effects of the standardized extracts of Panax ginseng (G115), Ginkgo biloba (GK501) and their combination Gincosan (PHL-00701). The extracts were administered orally for 7 days before training at three increasing doses: 17, 50, and 150 mg/kg for G115; 10, 30, and 90 mg/kg for GK501; and 27, 80, and 240 mg/kg for PHL-00701. The two extracts and their combination improved the retention of learned behavior. This effect varied considerably with the extracts, with the dose and with the behavioral method used. The results suggest that the Panax ginseng G115 and the Ginkgo biloba GK501 extracts possess properties similar in every respect to those of nootropic drugs. The favorable effects on learning and memory of the combination of G115 plus GK501 and the other pharmacological activities inherent in the extracts characterize this combination, offered as Gincosan as a particularly promising drug in geriatric practice.

Aging↗

Immunostimulating effects of acidic polysaccharides extract of Panax ginseng on macrophage function.

The root of Panax ginseng C. A. Meyer is one of the most popular natural tonics in oriental countries. In this study, we have isolated polysaccharide fraction of Panax ginseng (ginsan) and examined its effect on the function of murine peritoneal macrophages. When macrophages were treated with ginsan, cytotoxic activity against B16 melanoma cells was significantly induced. In addition, the levels of cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6 and Interferon-gamma (IFN-gamma) were increased and the production of reactive oxygen/nitrogen components such as nitric oxide (NO) and hydrogen peroxide (H2O2) was enhanced. Moreover, phagocytic activity was induced in ginsan-treated macrophages compared to the control. The expression of CD14 and 1-Ab on murine peritoneal macrophages was increased by the treatment with ginsan, while the expression of CD11b was decreased. Taken together, these results suggest that ginsan has an immunopotentiating effects on macrophages and these abilities could be used clinically for the treatment of diseases such as cancer.

Adjuvants, Immunologic↗

Enhanced triterpene and phytosterol biosynthesis in Panax ginseng overexpressing squalene synthase gene.

Roots of Panax ginseng, one of the most famous medicinal plants, contain various phytosterols and bioactive triterpene saponins (ginsenosides). In P. ginseng, phytosterols and triterpenes share the common biosynthetic intermediate, squalene. Here, we investigate the regulatory role of Panax ginseng squalene synthase (PgSS1) on the biosynthesis of phytosterols and triterpene saponins. PgSS1 transcripts are expressed ubiquitously in the various plant tissues, but higher in shoot apex and root. The transcript levels of PgSS1 increased markedly in the adventitious roots during 12- to 96-h period after metyl jasmonate (MeJA) treatment; MeJA treatment induced the activation of the transcripts of squalene epoxidase (SE), beta-amyrin synthase (bAS), but not cycloartenol synthase (CAS). Unlike MeJA treatment, overexpression of PgSS1 in adventitious roots of transgenic P. ginseng was followed by the up-regulation of all the downstream genes tested, such as SE, bAS, and CAS. The enhanced activity of PgSS1 enzyme resulted in remarkable increase of phytosterols as well as ginsenoside contents. These results demonstrate that PgSS1 is a key regulatory enzyme not only for phytosterol but also for triterpene biosynthesis and overexpressing of PgSS1 confers the hyperproduction of triterpene saponins to P. ginseng.

Acetates↗

Effect of panax notoginseng extracts on inferior sperm motility in vitro.

The purpose of this study was to investigate the effects of Panax notoginseng extracts on inferior sperm motility in vitro. Semen samples were collected from 23 patients with sperm motility between 20% and 40%. The sperm count was over 20 x 10(6)/ml in accordance with the World Health Organization standard. 1.0 mg/ml and 2.0 mg/ml of Panax notoginseng extracts including aqueous extract, n-butanol extract, and polysaccharide fraction on sperm motility and progression were evaluated by computer assisted semen analysis. The results demonstrated that sperm motility as well as progression on inferior sperm motility were enhanced at 1 hour and 2 hours after incubation with all three types of extracts.

Adult↗

Panax ginseng extract improves the scopolamine-induced disruption of 8-arm radial maze performance in rats.

The effects of Panax ginseng ethanol extract and its water (WSF)- and lipid-soluble (LSF) fractions on the scopolamine-induced disruption of radial maze performance in rats were examined. Ginseng root was refluxed with ethanol, and WSF and LSF were prepared from this ethanol extract. Scopolamine (0.075-0.3 mg/kg, i.p.) dose-dependently impaired the maze performance. However, the oral administration of Panax ginseng ethanol extract and WSF (2-8 g dried root/kg) 90 min before testing improved the maze performance disrupted by scopolamine (0.3 mg/kg) in a dose-dependent manner, but LSF failed to attenuate the disruption. These data suggest that ginseng extract possesses a beneficial effect regarding spatial cognitive impairment and that the water-soluble fraction of ginseng extract mainly contributes to the effect of the ethanol extract.

Animals↗