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Spinal cord injury (SCI) is defined as damage to the spinal cord that temporarily or permanently changes its function. There is no definite treatment established for neurological complete injury patients. This study investigated the effect of ginseng extract and ginsenosides on neurological recovery and antioxidant efficacies in rat models following SCI and explore the appropriate dosage. Searches were done on PubMed, Embase, and Chinese databases, and animal studies matches the inclusion criteria were selected. Pair-wise meta-analysis and subgroup analysis were performed. Ten studies were included, and the overall methodological qualities were low quality. The result showed ginseng extract and ginsenosides significantly improve neurological function, through the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale (pooled MD = 4.40; 95% CI = 3.92 to 4.88; p, Graphical abstract Image 1

We investigated if Red ginseng extract (RGE) suppressed monosodium urate crystal (MSU)-induced NLRP3 activation and could be a potential therapeutic agent for gout. The effects of RGE on acute gouty inflammation were investigated using the air-pouch model. RGE significantly suppressed acute gout inflammation in the air-pouch model, based on the decreased number of WBCs in the air-pouch lavage fluid. In vitro, RGE inhibited MSU-induced IL-1β production in THP-1 cells. Twenty-four gout patients in intercritical period were randomized either to red ginseng tablet (RGT) or placebo group. The assembly of NLRP3 inflammasomes was inhibited via reduced ASC expression and oligomerization. Patients taking RGT for 3 months showed significantly reduced NLRP3 expression compared to baseline. In conclusion, RGE suppressed acute gout inflammation by suppressing NLRP3 inflammasomes in animal models. Clinically, RGT suppressed NLRP3 expression in gout patients. The data suggest that red ginseng may exert an additive benefit in gout treatment.

We aimed to investigate ginsenoside pharmacokinetics in mice and rats following the repeated oral administration of red ginseng extract (RGE) (2 g/kg/day for 7 days). In mouse plasma, seven protopanaxadiol (PPD)-type ginsenosides (20(S)-ginsenoside Rb1, Rb2, Rc, Rd, Rg3, 20(S)-compound K, and 20(S)-PPD) and one protopanaxatriol (PPT)-type 20(S)-ginsenoside Re were detected, whereas 20(S)-ginsenoside Rb1, Rb2, Rc, Rd, 20(S)-PPD, and 20(S)-PPT were detected in rat plasma. The tetra- or tri-glycosylated PPD-type ginsenosides Rb1, Rb2, Rc, and Rd, high content ginsenosides in RGE, showed high plasma exposure, a short absorption time (Tmax), and a long elimination time (T1/2) among the ginsenosides detected in both species. Among the deglycosylated metabolites existing in the feces, 20(S)-compound K and 20(S)-PPD in mice and 20(S)-PPD and 20(S)-PPT in rats were found in the plasma samples. In addition to the differences in the ginsenosides detected in mice and rats, the Tmax and T1/2 of 20(S)-PPD and 20(S)-PPT in rats were greater than those in mice, suggesting the species-dependent difference in the gut metabolism and absorption of ginsenosides in the pathway from 20(S)-ginsenoside Rd to 20(S)-PPD and from 20(S)-ginsenoside Re to 20(S)-PPT. In conclusion, the choice of animal model should be the subject of careful consideration when exploring the pharmacology of RGE with specific focus on the plasma profile of an individual ginsenoside.

Objective To explain the phenomenon that Panax ginseng is not compatible with Raphani Semen based on pharmacodynamics and pharmacokinetics. Methods The forced swimming time and biochemical parameters such as blood lactate (BLA), serum urea nitrogen (SUN), and hepatic glycogen (GLU) were determined for anti-fatigue experiment. The UPLC-MS/MS was used to analyze the pharmacokinetics of Rg1, Re, Rb1, and Rd after orally administration of P. ginseng and P. ginseng combined with Raphani Semen to rats. Pharmacokinetic differences of four ginsenosides between single uses of P. ginseng and combined with Raphani Semen were investigated. Results The results showed that Raphani Semen tended to significantly reduce the anti-fatigue activity of P. ginseng. Co-administration of P. ginseng and Raphani Semen had significant effects on the pharmacokinetics of the four ginsenosides in rats compared to that observed with P. ginseng extract alone. The AUC0–12 h values of the four ginsenosides in PG group were higher than the corresponding values in the PR group. It can be inferred that Raphani Semen decreased the blood exposure of the four ginsenosides in rats when it combined with P. ginseng. Conclusion The anti-fatigue activity and pharmacokinetic results showed that Raphani Semen may reduce the pharmacological actions of P. ginseng.

The purpose of this study is to investigate the effect of fermented ginseng extract by Lactobacillus brevis (FGE) on lipopolysaccharide (LPS)-activated macrophages and 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated dermatitis in mice. FGE showed better anti-inflammatory activities than ginseng extract on the formation of nitric monooxide, IL-6, TNF-α, and IL-10 within non-cytotoxicity range in LPS-activated RAW264.7 cells. In addition, FGE reduced the expression of cyclooxygenase-2 and inducible nitric oxide synthase through inhibiting nuclear translocation of NF-κB. Consistent with in vitro experiments, FGE dose-dependently suppressed ear edema, and formation of TNF-α and IL-6, and it (50 mg/mL) significantly enhanced IL-10 level in ear tissues of TPA-treated mice. In conclusions, FGE has anti-dermatitic activity through inhibiting the activation of macrophages. Such effects of FGE are associated with suppressing nuclear translocation of NF-κB. Therefore, the features of FGE may provide the information for its application for therapy and prevention of dermatitis.

GS-E3D is an enzymatically modified ginseng extract by pectin lyase. In this study, we evaluated the preventive effects of GS-E3D on blood-retinal barrier (BRB) leakage in a rat model of diabetes. To produce diabetes, rats were injected with streptozotocin. GS-E3D was orally gavaged at 25, 50, and 100 mg/kg body weight for 6 weeks. We then compared the effect of GS-E3D with that of an unmodified ginseng extract (UGE) on retinal vascular leakage. The administration of GS-E3D significantly blocked diabetes-induced BRB breakdown. Immunofluorescence staining showed that GS-E3D reduced the loss of occludin in diabetic rats. In TUNEL staining, the number of apoptotic retinal microvascular cells was dose dependently decreased by GS-E3D treatment. GS-E3D decreased the accumulations of advanced glycation end products in the retinal vessels. In addition, the inhibition potential of GS-E3D on BRB breakage was stronger compared with UGE. These results indicate that GS-E3D could be a beneficial treatment option for preventing diabetes-induced retinal vascular injury.

The present study investigated the in vivo neuroprotective role of Panax ginseng extract (PGE) pretreatment against transient cerebral ischemia in a middle cerebral artery occlusion (MCAO) model. Rats were randomly divided as follows: group I, control; group II, sham-operated; group III, where animals were subjected to MCAO surgery; and group IV, where animals were orally administered 10 mL PGE per day (200 mg/kg of body weight per day) for 30 d followed by MCAO induction at day 31. Following 24 h of reperfusion, blood and tissue (brain, liver, and kidney) samples were collected for biochemical and histopathological examination. Biochemical testing included lipid profile, liver enzymes, kidney function tests, C-reactive protein (CRP), lactate dehydrogenase (LDH), glucose, and total protein estimation. Tissue antioxidants (catalase, superoxide dismutase, and glutathione) were assessed in brain, liver, and kidney tissues. MCAO-induced histopathological changes were also examined in the tissues. Pretreatment with PGE showed significant improvement in tissue antioxidant status in brain, liver and kidney tissues. PGE treatment maintains plasma lipid profile, liver enzymes, kidney function, and CRP, LDH, and glucose levels. Histologically, monocytes and macrophage infiltration were observed in the tissues of MCAO animals, whereas PGE treatment preserved tissue architecture and minimal monocyte infiltration. PGE supplementation showed a neuroprotective effect against ischemia–reperfusion injury by effectively increasing endogenous antioxidant enzyme activity.

Background Cancer cachexia is a severe condition that leads to the death of advanced cancer patients, and approximately 50~80% of cancer patients have cancer cachexia. Ginseng extract has been reported to have substantial anticancer and immune-enhancing effects; however, no study has reported the use of ginseng alone to treat cancer cachexia. Our study’s purpose was to investigate the therapeutic effects of ginseng-related monomers or mixtures on a cancer cachexia mouse model. Methods We selected BALB/c mice and injected the mice subcutaneously with C26 colon cancer cells to construct a cancer cachexia experimental animal model. The water extract of ginseng (WEG), two types of ginseng extracts (ginsenosides at doses of 5 mg/kg (GE5) and 50 mg/kg (GE50)) and ginsenoside Rb1 (Rb1) were used to treat cancer cachexia mice. Enzyme-linked immunosorbent assays (ELISAs) were used to analyze the inhibitory effects on two key inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Results Our experimental results show that GE5, GE50 and Rb1 significantly reduced the levels of TNF-α (P P Conclusions These results indicate that GE5, GE50 and Rb1 may be useful for reducing symptoms due to inflammation by reducing the TNF-α and IL-6 cytokine levels in cancer cachexia mice, thereby ameliorating the symptoms of cancer cachexia. Our results may be beneficial for future studies on the use of Chinese herbal medicines to treat cancer cachexia.

Background: We investigated the tolerability and pharmacokinetic properties of various ginsenosides, including Rb1, Rb2, Rc, Rd, and compound K, after single or multiple administrations of red ginseng extract in human beings. Methods: Red ginseng extract (dried ginseng > 60%) was administered once and repeatedly for 15 days to 15 healthy Korean people. After single and repeated administration of red ginsengextract, blood sample collection, measurement of blood pressure and body temperature, and routine laboratory test were conducted over 48-h test periods. Results: Repeated administration of high-dose red ginseng for 15 days was well tolerated and did not produce significant changes in body temperature or blood pressure. The plasma concentrations of Rb1, Rb2, and Rc were stable and showed similar area under the plasma concentration-time curve (AUC) values after 15 days of repeated administration. Their AUC values after repeated administration of red ginseng extract for 15 days accumulated 4.5- to 6.7-fold compared with single-dose AUC. However, the plasma concentrations of Rd and compound K showed large interindividual variations but correlated well between AUC of Rd and compound K. Compound K did not accumulate after 15 days of repeated administration of red ginseng extract. Conclusion: A good correlation between the AUC values of Rd and compound K might be the result of intestinal biotransformation of Rb1, Rb2, and Rc to Rd and subsequently to compound K, rather than the intestinal permeability of these ginsenosides. A strategy to increase biotransformation or reduce metabolic intersubject variability may increase the plasma concentrations of Rd and compound K. Keywords: ginsenosides, pharmacokinetics, red ginseng, single and repeated administration, tolerability

In this study, we precisely showed how the Rg3-enriched red ginseng extract (Rg3-RGE) lowers glucose, triglyceride, and low-density lipoprotein (LDL) levels in LDL–/– mice. Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase), alanine aminotransferase /serum glutamate-pyruvate transaminase, and steatohepatitis were found to be reduced, and atheroma formation was inhibited by Rg3-enriched red ginseng extract. Keywords: antiatheromatic, antidiabetic, antihypercholesterolemic, Rg3-enriched Korean Red Ginseng extract

Radiation therapy is associated with liver damage and late liver injury. The hepatoprotective effect of Korean Red Ginseng (KRG) was determined in whole-body gamma-irradiated (γIR) mice. KRG at a dose of 10 and 50 mg/kg body weight was administrated to male C57BL/6 mice (each group, n=5) intraperitoneally for five days before whole-body γIR (6.5 Gy). Three days after γIR, serum and liver tissue were collected and analysed. Pretreatment with KRG suppressed serum alkaline phosphatase (ALP), alkaline aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl-transferase (GGT) activities. It also caused a marked increase in cyclooxygenase-2 (COX-2) and tumour growth factor-β1 (TGF-β1) expression associated nuclear factor-κB (NF-κB) activation in the liver. Extracellular signal-regulated kinases (ERKs) were also activated by irradiation. KRG treatment before irradiation could strongly suppress COX-2, TGF-β1, and ERK activation in the liver. Pretreatment with KRG may alleviate the severity of radiation-induced liver injury and fibrosis.

Ginseng is known as the “king” of herbal plants and has been used widely in Asia for centuries. Ginseng contains active saponins, including protopanaxadiols, protopanaxatriols, and other compounds. There are many methods for processing ginseng, such as steaming, fermentation, expansion, and conversion of active compounds, which can improve its biological activity. In this study, we investigated the cytotoxic and oxidative effects of fermented black color ginseng (FBCG), black ginseng (BG), and white ginseng (WG) on a human lung carcinoma cell line (A549). Moreover, we found that treatment with FBCG induced oxidative stress in the A549 cell line and increases the apoptosis percentage; these effects were linked to the stimulation of the caspase 3/mitogen-activated protein kinase (caspase 3/MAPK) pathway. We also evaluated the anti-coronavirus disease-2019 (COVID-19) effect of FBCG on a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected Vero E6 cell line. Our results suggest that FBCG not only inhibits the replication of this strain of virus in the cell but also reduces the number of viral RNA (vRNA) copies in the extracellular environment. Taken together, these data show that FBCG has both potential anti-lung cancer and anti-COVID-19 effects.

Background: Korean Red Ginseng has been used for several decades to treat many diseases, enhancing both immunity and physical strength. Previous studies have documented the therapeutic effects of ginseng, including its anticancer, antiaging, and anti-inflammatory activities. These activities are mediated by ginsenosides present in the ginseng plant. Ginsenoside Rg3, an effective compound from red ginseng, has been shown to have antiplatelet activity in addition to its anticancer and anti-inflammatory activities. Platelets are important for both primary hemostasis and the repair of the vessels after injury; however, they also play a crucial role in the development of acute coronary diseases. We prepared ginsenoside Rg3-enriched red ginseng extract (Rg3-RGE) to examine its role in platelet physiology. Methods: To examine the effect of Rg3-RGE on platelet activation in vitro, platelet aggregation, granule secretion, intracellular calcium ([Ca2+]i) mobilization, flow cytometry, and immunoblot analysis were carried out using rat platelets. To examine the effect of Rg3-RGE on platelet activation in vivo, a collagen plus epinephrine-induced acute pulmonary thromboembolism mouse model was used. Results: We found that Rg3-RGE significantly inhibited collagen-induced platelet aggregation and [Ca2+]i mobilization in a dose-dependent manner in addition to reducing ATP release from collagen-stimulated platelets. Furthermore, using immunoblot analysis, we found that Rg3-RGE markedly suppressed mitogen-activated protein kinase phosphorylation (i.e., extracellular stimuli-responsive kinase, Jun N-terminal kinase, p38) as well as the PI3K (phosphatidylinositol 3 kinase)/Akt pathway. Moreover, Rg3-RGE effectively reduced collagen plus epinephrine-induced mortality in mice. Conclusion: These data suggest that ginsenoside Rg3-RGE could be potentially be used as an antiplatelet therapeutic agent against platelet-mediated cardiovascular disorders.

Background Red ginseng oil (RGO) is produced by supercritical CO 2 extraction of secondary products derived from Korean Red Ginseng extract. As the use of RGO has increased, product safety concerns have become more important. Methods In the present study, the subacute oral toxicity and bacterial reverse mutagenicity of RGO were evaluated. Sprague–Dawley rats were orally administered with RGO for 28 d by gavage. Daily RGO dose concentrations were 0 mg/kg body weight (bw), 500 mg/kg bw, 1,000 mg/kg bw, or 2,000 mg/kg bw per day. Bacterial reverse mutation tests included five bacterial strains ( Escherichia coli WP2 and Salmonella typhimurium TA98, TA100, TA1535, and TA1537), which were used in the presence or absence of metabolic activation. The plated incorporation method for mutation test was used with RGO concentrations ranging from 312.5 μg to 5,000 μg per plate. Results The subacute oral toxicity test results did not reveal any marked changes in clinical characteristics. There were no toxicological changes related to RGO administration in hematological and serum biochemical characteristics in either control or treatment animals. Furthermore, no gross or histopathological changes related to RGO treatment were observed. The bacterial reverse mutation test results did not reveal, at any RGO concentration level and in all bacterial strains, any increase in the number of revertant colonies in the RGO treatment group compared to that in the negative control group. Conclusion The no-observed-adverse-effect level of RGO is greater than 2,000 mg/kg bw and RGO did not induce genotoxicity related to bacterial reverse mutations.

Background In general, after Panax ginseng is administered orally, intestinal microbes play a crucial role in its degradation and metabolization process. Studies on the metabolism of P. ginseng by microflora are important for obtaining a better understanding of their biological effects. Methods In vitro biotransformation of P. ginseng extract by rat intestinal microflora was investigated at 37°C for 24 h, and the simultaneous determination of the metabolites and metabolic profile of P. ginseng saponins by rat intestinal microflora was achieved using LC–MS/MS. Results A total of seven ginsenosides were detected in the P. ginseng extract, including ginsenosides Rg1, Re, Rf, Rb1, Rc, Rb2, and Rd. In the transformed P. ginseng samples, considerable amounts of deglycosylated metabolite compound K and Rh1 were detected. In addition, minimal amounts of deglycosylated metabolites (ginsenosides Rg2, F1, F2, Rg3, and protopanaxatriol-type ginsenosides) and untransformed ginsenosides Re, Rg1, and Rd were detected at 24 h. The results indicated that the primary metabolites are compound K and Rh1, and the protopanaxadiol-type ginsenosides were more easily metabolized than protopanaxatriol-type ginsenosides. Conclusion This is the first report of the identification and quantification of the metabolism and metabolic profile of P. ginseng extract in rat intestinal microflora using LC–MS/MS. The current study provided new insights for studying the metabolism and active metabolites of P. ginseng .

Hydroxyurea (HU) is an anti-neoplastic drug which is used for treatment of many types of tumors; however, its wide range of deleterious effects may limit its medical usage. This study was conducted to assess the possible protective role of Panax ginseng extract (Ginseng) against HU- induced hepato-renal damage in rats. Forty male Wistar albino rats were randomly divided into four equal groups (10 rats each). Group I (control) received 1ml purified water. Group II (Ginseng-treated) received 200 mg/kg body weight (b.wt) of Panax ginseng extract. Group III (HU-treated) received HU at a dose of 500 mg/ kg b.wt. Group IV (HU plus ginseng) received HU and Panax ginseng extract in similar doses of group II and III. All the treatments were administrated orally. Treatment with Panax ginseng failed to ameliorate the hematological alterations caused by HU, but, its ability to alleviate hepato-renal cytotoxic effect was proved through significant reduction in plasma level of hepato-renal injury biomarkers (AST, ALT, GGT, urea and creatinine) which were elevated in HU-treated group. Also, this effect was affirmed by decreased level of plasma pro-inflammatory cytokines (TNF-I± and IL-6) and enhanced anti-oxidant state (decreased MDA content and increased GPX activity) of hepato-renal tissues upon Panax ginseng extract administration with HU. Histopathologically, HU induced impairments in both hepatic and renal tissues of the treated rats. Conversely, concurrent administration of ginseng with HU partially improved these alterations. Key words : hydroxyurea; hepato-renal toxicity; Panax ginseng; rats

This study investigates the modulating effect of ginseng against testicular toxicity, oxidative stress and changes in some biochemical parameters induced by doxorubicin. Twenty male rats were divided into four groups. The 1st group received distilled water orally (control group), The 2nd group received doxorubicin (5 mg/kg b.wt. intrapertenoineal) once a week for eight weeks, The 3rd group received ginseng extract (200 mg/kg b.wt.) daily for eight weeks and the 4th group received doxorubicin with ginseng extract by the same doses as in the 2nd and the 3rd groups respectively. At the end of the 8th week, blood and semen samples were taken for biochemical and semen analysis, respectively. The doxorubicin treated group had significantly higher serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), Creatine kinase (CK) and lactate dehydrogenase (LDH) along with lower levels of total protein, albumin and globulin. In addition, a significant decrease in antioxidant enzymes (SOD, CAT, GSHPx), and glutathione (GSH) associated with higher level of malondialdehyde (MDA) were observed. At the same time, the group that took doxorubicin with ginseng did not differ from control group in terms of these parameters. Male fertility study showed changes in testosterone and semen analysis in both groups treated with doxorubicin, while the group that took doxorubicin with ginseng showed an improvement towards control levels of these parameters. Thus ginseng supplement can reduce the negative effects of doxorubicin- induce.

Background: Anticancer agents induce a variety of adverse effects when administered to cancer patients. Busulfan is a known antileukemia agent. When administered for treatment of leukemia in young patients, busulfan could cause damage to the male reproductive system as one of its adverse effects, resulting in sterility. Methods: We investigated the effects of Korean Red Ginseng extract (KRGE) on busulfan-induced damage and/or dysfunction of the male reproductive system. Results: We found that administration of busulfan to mice: decreased testis weight; caused testicular histological damage; reduced the total number of sperm, sperm motility, serum testosterone concentration; and eventually, litter size. Preadministration of KRGE partially attenuated various busulfan-induced damages to the male reproductive system. These results indicate that KRGE has a protective effect against busulfan-induced damage to the male reproduction system. Conclusion: The present study shows a possibility that KRGE could be applied as a useful agent to prevent or protect the male reproductive system from the adverse side effects induced by administration of anticancer agents such as busulfan.

본 연구는 건강보조제 및 약제로서 전신의 염증반응 및 여러 약리적 효능을 가지고 있는 홍삼이 국소적인 안면 통증의 완화에 영향을 끼치는지에 관해 조사하였다. 실험동물은 4그룹으로 대조군(n=6)과 5% 포르말린 주입군(n=6), 5% 포르말린+D.W. 주입군, 홍삼(4.5 ml)(n=6) 복용군으로 나누어 45분간 안면을 긁거나 문지르는 행위를 계수하여 비교하였다. 홍삼 복용군에서 포르말린 주입군에 비해 유의하게 긁거나 문지르는 행위가 줄어들었으며, 15분부터 통증완화효과가 증가되기 시작되어 30분까지 유의한 효과를 보였다. 홍삼투여군에 대한 단백질정량분석 (western blot)으로 통증유발기전에 연관되는 염증과 항산화, NO생성에 관련된 신호전달 단백질 p38 MAPK와 iNOS, Nrf2를 뇌, 연수에서 활성정도를 비교한 결과 감소하는 경향을 확인할 수 있었다. 이상의 결과들은 홍삼이 전신적 약리효과 뿐만 아니라 국소적인 염증, 통증완화에도 효능이 있음 나타낸다. 【The effects of korean red ginseng (KRG) extracts on orifacial pain control in terms of the systemic inflammatory response and pharmacological effects as health supplements were investigated. The experimental group were divided into three groups, the control group (n=6), formalin (5%, $50{\mu}{\ell}$ ) injection group (n=6), and formalin (5%, $50{\mu}{\ell}$ ) injection added KRG administrated group (4.5 ml/kg, n=6). The KRG administrated group prior to the formalin injection significantly attenuated the behavioral response compared to that of the control group. Pain reduction was suppressed mainly from 15 min to 30 min. The KRG administrated rats showed significantly reduced p38 MAPK, iNOS and Nrf2 expression in the brain and medulla oblongata according to Western blot analysis. These findings suggest that KRE may have a useful effect on orificial pain control functions by preventing the p38 MAPK pathway.】

ABSTRACT: Aim: This study investigated the protective effect of a standardized extract of Panax ginseng on multiple cisplatin-induced ‘sickness behaviors’ (model of cancer-induced cachexia) in rats. Materials & methods: Cisplatin was administered twice weekly (1–2 mg/kg, intraperitoneal) for 5 consecutive weeks. Panax ginseng extract (0, 25 and 50 mg/kg, intragastric) was administered daily over the 5-week period of cisplatin exposure. Malaise, bodyweight and temperature, pain sensitivity, and endurance running were recorded at baseline and at 5 weekly intervals. Results: Treatment with cisplatin produced severe signs of malaise, marked loss of bodyweight, hypothermia, hyperalgesia and reduction in running time. Treatment with Panax ginseng extract completely prevented all cisplatin-induced alterations. Conclusion: These data indicate that treatment with Panax ginseng extract exerted a protective effect in a rat model of cachexia and suggest that Panax ginseng extract may be a therapeutic promising tool for supportive care in oncology.

The present study was designed to investigate the cardioprotective effects of Korean Red Ginseng extract (KRG) on isoproterenol (ISO)-induced cardiac injury in rats, particularly in regards to electrocardiographic changes, hemodynamics, cardiac function, serum cardiac enzymes, components of the myocardial antioxidant defense system, as well as inflammatory markers and histopathological changes in heart tissue. ISO (150 mg/kg, subcutaneous, two doses administered at 24-hour intervals) treatment induced significant decreases in P waves and QRS complexes (p0.05). Our results suggest that KRG significantly protects against cardiac injury and ISO-induced cardiac infarction by bolstering antioxidant action in myocardial tissue.

Korean red ginseng (KRG) is prepared by the process of steaming the roots of Panax ginseng. In this study, the feeding effects of KRG-water extract (KRGE) on ethanol-induced liver damage were elucidated by measuring serum biomarkers in rats. Serum γ-glutamyltranspeptidase (γ-GT) activity and the concentration of malondialdehyde (MDA) were significantly increased by short-term and long-term ethanol treatment in rats, whereas the activities of serum glutamate pyruvate transaminase (GPT) and glutamate oxaloacetate transaminase (GOT) did not respond. Pretreatment with KRGE maintained the activity of serum GPT, and the MDA concentration induced by short-term ethanol ingestion remained within the normal range. However, co-feeding of KRGE to rats decreased the concentration of MDA but failed to modulate the serum γ-GT activity induced by long-term ethanol treatment. Our studies suggest that in rats, it appears that KRGE does not sufficiently reverse the physiological response evoked by long-term ethanol ingestion to maintain normal conditions, in view of the serum biomarker γ-GT, regardless of KRGE’s favorable antioxidant activity.

The roots of Panax ginseng (ginseng) have been extensively used in traditional Chinese medicine. However, herb-drug interactions between ginseng and other co-administered drugs are not fully understood concerning the effect of ginseng on drug metabolism and clearance. The current study aimed to elucidate the effect of total ginsenosides, a typical ginseng extract, on the regulation of Cyp1a2, a key enzyme to regulate drug metabolism under the normal and inflammatory conditions in mice. Female C57BL/6J mice treated with vehicle and lipopolysaccharide (LPS) were intragastrically administered ginseng extract for 7 days before hepatic P450 expression was analyzed. Primary mouse hepatocytes were also employed to further explore the effects of total ginsenosides on Cyp1a2 expression. The results showed that total ginsenosides in P. ginseng extract exhibited a concentration-dependent suppression on Cyp1a2 mRNA and protein level in both mice and primary mouse hepatocytes. Notably, the inhibitory effects of total ginsenosides on Cyp1a2 mRNA and protein expression were further enhanced following LPS treatment. Therefore, future research is warranted to investigate the role of ginsenosides in the regulation of hepatic CYP450s. Moreover, consumption of ginseng as food or supplement should be monitored for patients on combinational therapy, especially those with inflammatory diseases.

To evaluate the pharmacokinetics of compound K after oral administration of HYFRG and RG in humans, an open-label, randomized, single-dose, fasting, and one-period pharmacokinetic study was conducted. After oral administration of a single 3 g dose of HYFRG and RG to 24 healthy Korean males, the mean (±SD) ofAUC0–tandCmaxof compound K from HYFRG were 1466.83 ± 295.89 ng·h/mL and 254.45 ± 51.20 ng/mL, being 115.2- and 80-fold higher than those for RG (12.73 ± 7.83 ng·h/mL and 3.18 ± 1.70 ng/mL), respectively; in case of Sprague Dawley rats the mean (±SD) ofAUC0–tandCmaxof compound K from HYFRG was 58.03 ± 32.53 ng·h/mL and 15.19 ± 10.69 ng/mL, being 6.3- and 6.0-fold higher than those from RG (9.21 ± 7.52 ng·h/mL and 2.55 ± 0.99 ng/mL), respectively.Tmaxof compound K in humans and rats was 2.54 ± 0.92 and 3.33 ± 0.50 h for HYFRG and 9.11 ± 1.45 and 6.75 ± 3.97 hours for RG, respectively. In conclusion, the administration of HYFRG resulted in a higher and faster absorption of compound K in both humans and rats compared to RG.

To evaluate the difference in expressing pharmacological effects of ginseng by intestinal microflora between Koreans, metabolic activities of ginseng, ginsenoside Rb1 and Rg1 by 100 fecal specimens were measured. The β-glucosidase activity for p-nitrophenyl- β-D-glucopyranoside was 0 to 0.42 μmol/min/mg and its average activity (mean±SD) was 0.10±0.07 μmol/min/mg. The metabolic activities of ginsenosides Rb1 and Rg1 were 0.01 to 0.42 and 0.01 to 0.38 pmol/min/mg, respectively. Their average activities were 0.25±0.08 and 0.15±0.09 pmol/min/mg, respectively. The compound K-forming activities from ginsenoside Rb1 and ginseng extract were 0 to 0.11 and 0 to 0.02 pmol/min/mg, respectively. Their average compound K-forming activities were 0.24±0.09 pmol/min/ mg and 2.14±3.66 fmol/min/mg, respectively. These activities all were not different between males and females, or between ages. Although compound K-forming activity from the aqueous extract of ginseng was low compared to that from ginenoside Rb1, their profiles were similar to those of isolated compounds. Based on these findings, we believe that the intestinal bacterial metabolic activities of ginseng components are variable in individuals and may be used as selection markers for responders to ginseng.

Zearalenone (ZEA) is a phenolic resorcylic acid lactone compound produced by several species of Fusarium. ZEA has toxic effects in the testes of domestic and laboratory animals. Korean red ginseng (KRG), the steamed root of Panax ginseng Meyer, has multiple pharmacological effects such as vasorelaxation, anti-thrombosis, anti-hypertension, etc. In this study, we investigated the effects of KRG extract on testicular toxicity induced by ZEA. Rats were treated with 300 mg/kg oral doses of KRG for 4 weeks every other day. The rats were then treated with a single dose of 5 mg/kg ZEA delivered intraperitoneally, whereas control rats received only doses of the vehicle. As a result, germ cell apoptosis induced by ZEA was decreased by KRG pre-treatment. In addition, Fas and Fas-L expression was reduced in rats that received KRG pre-treatment compared to ones treated with ZEA alone. In conclusion, impaired spermatogenesis resulting from ZEA treatment was prevented by KRG through Fas-Fas L modulating.

A lipid-soluble ginseng extract possesses an anticancer activity against advanced human lung tumors in an established murine xenograft model without any sign of toxicity. The extract also shows a potent anti-proliferative activity against human cancer cell lines, leading to expansion of its preclinical applications to specific human tumor types.

－ We tested whether ginsenosides Rg 3 -standardized ginseng extract (RGE) has anti-stress effects in restraint-stressed animals. RGE increased time spent in the open arms and open arm entries in the elevated plus-maze test. In addition, RGE blocked the reduction of center zone distance and stereotypes behaviors in the open-field test. RGE also increased head dips in stressed mice, indicating anxiolytic-like effects. Stress decreased movement distance and duration, burrowing, and rearing frequency but increased face washing and grooming. RGE significantly reversed burrowing and rearing activity in stressed mice. In addition, we measured sleep architecture in restraint stressed rats using EEG recorder. Stress increased rapid eye movement (REM) sleep, but total sleep and non-rapid eye movement (NREM) sleep were not changed. RGE did not affect sleep architecture in stressed rats. These behavioral experiments suggest that RGE has anti-stress effects in restraint-stressed animal models.Keywords: Anti-stress, Ginsenoside Rg

Lipid-soluble ginseng extract was prepared by n-hexane extraction of red ginseng. BALB/c-nu mice were inoculated with human lung cancer (NCI-H460) cells to establish a human tumor xenograft model in nude mice, and the lipid-soluble ginseng extract was orally administered. The tumor inhibitory rates of the lipid-soluble ginseng extract at doses of 0.1, 0.3, and 1.0 g/kg/day were 18.9% (P

Korean ginseng and mountain ginseng (Panax ginseng CA Meyer) are important traditional herbal plants whose ginsenosides are generally accepted as serving to improve sexual functions, such as penile erection. We investigated the effects of tissue-cultured mountain ginseng extract (TMGE) on male patients with erectile dysfunction (ED). A double-blind, placebo-controlled study was conducted with 143 patients experiencing ED. Over the course of 8 weeks, one group took 1 000 mg of TMGE twice a day, and the other group took 1 000 mg of placebo twice a day. The effects of the TMGE and the placebo were analyzed using the Korean version of the International Index of Erectile Function (IIEF) questionnaire. A total of 86 patients completed 8 weeks of treatment. The scores on the five domains of the IIEF after medication were significantly higher than the baseline scores in the group treated with TMGE (P < 0.05), whereas no significant improvement was observed in the placebo group (P > 0.05). Erectile function and overall satisfaction scores after medication were significantly higher in the TMGE group than in the placebo group (P < 0.05). Erectile function of patients in the TMGE-treated group significantly improved, suggesting that TMGE could be utilized for improving erectile function in male patients.

Lipid soluble ginseng extract was administered by oral route in doses of 600 ㎎/patient daily in cancer patients over 2 months and 6 months. The administration of ginseng extract in cancer patients maintained the ratio of CD4/CD8 and number of the natural killer cell in the normal range during the administration period. Also its administration showed a positive effect on tumor values in 87.5% of patients in 2 month-group and in 50% of patients in 6 month-group, as determined by various cancer markers. Liver and kidney functions maintained normal condition during administration period of 6 months. Although there was no statistical significance, these data suggest that lipid soluble ginseng extract may be useful as an adjuvant therapeutic agent and nutritional supplement for the improvement of immune function and health in cancer patients. This study would provide the basis for the research in which the antitumor and immunopotential activity of lipid soluble ginseng extract for cancer patients are evaluated in formal clinical trial with statistically significant patient number.

Objectives The purpose of this study is to investigate the effects of cultivated wild ginseng extract on primary culturedpreadipocyte and adipocytes. Methods Diminish preadipocyte proliferation does primary role to reduce obesity. So, preadipocytes and adipocytes wereperformed on cell cultures with using Sprague-Dawley rats and treated with 0.01-1㎎/㎖cultivated wild ginsengextract. Result At all concentrations, cultivated wild ginseng extract wasn't show the suppress proliferation of preadipocytessignificantly and failed to show effects on decomposition of adipocytes except high dosage. Conclusion Based on these findings, cultivated wild ginseng is not a suitable choice for the treatment of localized obesity. key words Cultivated wild ginseng, preadipocytes, adipocytes, obesity. The Effect of Cultivated Wild Ginseng Extract on Preadipocyte Proliferation ※교신저자: 권기록, 강원도원주시우산동 283 상지대학교부속한방병원침구과(Tel: 033-741-9257 FAX: 033-730-0653 E-mail: beevenom@paran.com)※This research was supported by Sangji University Research Fund, 2006

In this study, we investigated the effects of Korean red ginseng water extract (KRGE) on hepatic lipid accumulation in HepG2 cells. KRGE decreased hepatic triglyceride and cholesterol levels. Further, KRGE suppressed expression of fatty acid synthase (FAS) and 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase. These results suggest that KRGE may reduce hepatic lipid accumulation by inhibition of FAS and HMG-CoA reductase expression in HepG2 cells.

Liver and kidney are specific organs which play an active role in biotransformation and detoxification mechanisms. Ant adverse effect of chemicals or heavy metal can cause the delay or fade in these mechanisms. Present study was designed to find out the protective effect of Panax ginseng extract on renal functions altered by mercuric chloride (heavy metal) in albino rat. Fifty albino rats were divided into 10 groups. Five groups for acute study and five groups for sud-acute study viz. control group (Tween 20 and distilled water), mercuric chloride treated group (0.926 ㎎/㎏ body wt. for acute and 0.044 ㎎/㎏ body wt. for sub-acute group after calculated LD?? (9.26 ㎎/㎏ body wt.) by probit analysis (Finney, 1971)¹, Panax ginseng extract treated group (10 ㎎/㎏ body wt. for acute and sub-acute sets), mercuric chloride treated followed by Panax ginseng extract and Panax ginseng extract followed by mercuric chloride group. All doses were given orally by gavage tube. The result revealed that the serum urea and creatinine significantly increased in mercuric chloride treated group, while significantly decreased (p＜0.01) in Panax ginseng extract group after acute and sub-acute treatment. The biochemical estimation is also confirmed by nephropathological aspect. However, the Panax ginseng extract treated followed by mercuric chloride group is more prominent than the mercuric chloride treated followed by Panax ginseng extract group. It can be concluded that Panax ginseng extract had a protective nature on renal functions against mercuric chloride toxicity in albino rats.

Adverse changes in individual’s biochemistry under heavy metal stress are directly linked with its metabolic activity and health status. The present investigation highlights the differences in protecting role of Panax ginseng extract against mercuric chloride induced alterations in serum proteins. The assessment was based on dividing fifty albino rats into two sets, one for acute and the other for sub-acute study. All the sets had five groups with five albino rats in each i.e. control group, mercuric chloride treated group, Panax ginseng extract treated group, mercuric chloride followed by Panax ginseng extract treated group and Panax ginseng extract followed by mercuric chloride treated group. Mercuric chloride was given orally 0.926 ㎎/㎏ body weight for acute set and 0.044 ㎎/㎏ body weight for sub-acute set after LD50 (9.26 ㎎/㎏ body weight) determination by probitt analysis. 10 ㎎/㎏ body weight Panax ginseng extract was given in both acute and sub-acute sets after incorporating safety trials. The control group received tween-20 and distilled water only. The result exhibited significantly reduction (P＜0.01) in serum protein, albumin and globulin following mercuric chloride intoxication whereas significant (P＜0.01) enhancement in other groups with Panax ginseng extract as an ingredient confirming its protective role. All serum samples were also electrophoresed in 10% SDS with standard marker using discontinuous buffering system. Gradual disappearance of alpha-2 and beta-1 globulin bands from electrophoretic pattern was observed, while a single sharp band was observed between beta-2 and gamma globulin in serum protein pattern of acutely mercuric chloride treated rats. However, this band could not be visualized in sub-acute studies. Panax ginseng extract exhibits a better protection after acute intoxication.

The ginseng root has been traditionally used as a sedative in oriental countries. However, the condition "ginseng abuse syndrome" (GAS), defined as hypertension, nervousness, sleeplessness, skin eruption, and morning diarrhea, was coined as a result of a study of people who had been using a variety of ginseng preparations. However, we reported that administration of RGE increased rapid eye movement (REM) and non rapid eye movement (NREM) sleep via GABAergic systems in animals. Therefore, this study was performed to investigate how red ginseng extract (RGE) affects sleeping behaviors in human volunteers.RGE (1500 mg) was orally administered to young male healthy volunteers (from 15 to 37 years old ages, n=15) three times a day for 7 days. Overnight polysomnographic (PSG) studies were performed two times, 1 day before and 7 days after RGE administration. We investigated differences in sleep architecture parameters such as total sleep time (TST), sleep efficacy (SE: total sleep time/time in bed), proportion of each sleep stage, and wakefulness after sleep onset (WASO) between baseline PSG and PSG after RGE administration.Total wake time (TWT) was significantly reduced (P0.05) and SE was increased (P0.05), although slow wave sleep stage 1 (N1) was reduced (P0.01) and non-rapid eye movement (REM) sleep was increased (P0.03) after administration.From these results, it is presumed that RGE intake would improve the quality of sleep, thus having beneficial effects on sleep disturbed subjects.

The results of a survey of the medicinal plants found in the herbal market of Thessaloniki, which comprises traditional shops, modern shops and open-air market stalls, are presented. A total number of 172 taxa, Pteridophyta and Spermatophyta, were found in 18 selected market spots. Information is provided on the origin, the plant parts used, the ways of drug preparation and the medicinal uses of the herbs found. The majority of them (133 taxa) are of Greek origin and are gathered from the wild (99). A remarkable number of herbs (93) found in the market of Thessaloniki are mentioned by Dioscurides whereas the comparison to the recent ethnobotanical information shows that the utilization of Dioscurides’ plants remains uninterrupted. Thus it is suggested that the herb trade is still based on the Greek ethnobotanical tradition, dating from antiquity.

Univ Estadual Paulista, UNESP, Inst Biosci, Lab Phytomed Pharmacol & Biotechnol PhytoPharmaTe, Botucatu, SP, Brazil

To investigate the adjuvant therapeutic effects of fermented red ginseng (FRG) extract on non-small cell lung cancer (NSCLC) patients treated with chemotherapy.A total of 60 patients with advanced NSCLC were divided into two groups using a random number table, i.e., the gemcitabine plus cisplatin (GP) chemotherapy alone group (26 patients) and the FRG + GP chemotherapy group (34 patients), for 60-day treatment. Patients were then assessed according to the Fatigue Symptom Inventory, Chinese medicine symptoms score, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Karnofsky Performance Status Scale, and Functional Assessment of Cancer Therapy-Lung. In addition, chemotherapy toxicity and tumor biomarkers were measured.For NSCLC patients after chemotherapy, FRG extract significantly improved the FSI score, CM symptoms score, psychological status, physical conditions, and quality of life and reduced chemotherapy toxicity, but the expression levels of carcinoembryonic antigen, cytokeratin-19 fragments, and neuron-specific enolase were not significantly different between the chemotherapy alone and the FRG + chemotherapy groups or between pre- and post-treatments.This study demonstrated that FRG extract had an adjuvant effect on advanced NSCLC patients treated with chemotherapy. Further studies with a larger sample size will verify the current findings.

Background: This study was performed to investigate whether ginseng extract has a protective effect in an experimental mouse model of chronic cyclosporine (CsA) nephropathy. Methods: Mice were treated with CsA (30 mg/kg/day, subcutaneously) with or without Korean red ginseng extract (KRG) (0.2, 0.4 g/kg/day, orally) on a 0.01% salt diet for 4 weeks. The effect of KRG on CsA-induced renal injury was evaluated by assessing renal function and pathology, mediators of inflammation, tubulointerstitial fibrosis and apoptotic cell death. Using an in vitro model, we also examined the effect of KRG on CsA-treated proximal tubular cells (HK-2). Oxidative stress was measured by assessing 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels in 24-hour urine, tissue sections, and culture media. Results: Four weeks of CsA treatment caused renal dysfunction, typical pathologic lesions and apoptotic cell death. KRG treatment reduced serum creatinine and blood urea nitrogen and histopathology and increased creatinine clearance. Proinflammatory and profibrotic molecules such as induced nitric oxide synthase, cytokines, transforming growth factor (TGF)-β1 and TGF-β1-inducible gene h3 and apoptotic cell death, also decreased with KRG treatment. Consistent with these results, in vitro studies showed that addition of KRG protected against CsA-induced morphological changes, cytotoxicity, inflammation, and apoptotic cell death as demonstrated by annexin V binding. These changes were accompanied by decrease in the level of 8-OHdG in urine and culture supernatant after KRG treatment. Conclusion: The results of our in vivo and in vitro studies demonstrate that KRG has a protective effect in CsA-induced renal injury via reducing oxidative stress.