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Ginsenoside Rh1 possesses antiallergic and anti-inflammatory activities.

BACKGROUND: Ginseng (the root of Panax ginseng C.A. Meyer, Araliaceae) has been reported to possess various biological activities, including anti-inflammatory and antitumor actions. In this study, we investigated the antiallergic activity of ginsenosides isolated from ginseng. METHOD: We isolated ginsenosides by silica gel column chromatography and examined their in vitro and in vivo antiallergic effect on rat peritoneal mast cells and on IgE-induced passive cutaneous anaphylaxis (PCA) in mice. The in vitro anti-inflammatory activity of ginsenoside Rh1 (Rh1) in RAW264.7 cells was investigated. RESULTS: Rh1 potently inhibited histamine release from rat peritoneal mast cells and the IgE-mediated PCA reaction in mice. The inhibitory activity of Rh1 (87% inhibition at 25 mg/kg) on the PCA reaction was found to be more potent than that of disodium cromoglycate (31% inhibition at 25 mg/kg); Rh1 was also found to have a membrane-stabilizing action as revealed by differential scanning calorimetry. It also inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression in RAW 264.7 cells, and the activation of the transcription factor, NF-kappaB, in nuclear fractions. CONCLUSION: The antiallergic action of Rh1 may originate from its cell membrane-stabilizing and anti-inflammatory activities, and can improve the inflammation caused by allergies.

Animals↗

Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach.

Systematic evidence regarding herb-drug interactions is lacking. This study investigated herb-drug interactions with warfarin. S-warfarin concentration and response (prothrombin complex activity) data from healthy subjects (n = 24) who received a single warfarin dose (25 mg) and either St John's wort, Asian ginseng, Ginkgo biloba, or ginger were analyzed using a population pharmacokinetic-pharmacodynamic modeling approach. The ratio of S-warfarin apparent clearance (CL/F) compared to control was 1.39 +/- 0.06 and 1.14 +/- 0.04 after St John's wort and Asian ginseng pretreatment, respectively. Other pharmacokinetic and pharmacodynamic parameters were unaffected. Coadministration of St John's wort significantly increased S-warfarin CL/F, whereas treatment with Asian ginseng produced only a moderate increase in CL/F. Ginkgo and ginger did not affect the pharmacokinetics of warfarin in healthy subjects. None of the herbs studied had a direct effect on warfarin pharmacodynamics. Studies in anticoagulated patients are warranted to assess the clinical significance of these herb-drug interactions.

Adult↗

Anxiolytic-like effects of ginsenosides on the elevated plus-maze model in mice.

In a previous study, we reported that ginseng extract has anxiolytic-like effects in the elevated plus-maze model and that the ginseng saponin fraction plays an important role. This experiment was performed to investigate the anxiolytic-like effects of ginsenosides Rb1, Rg1, Rg3-R, and Rg3-S, and the Rg5 and Rk mixture isolated from the ginseng saponin fraction in the elevated plus-maze. Furthermore, the anxiolytic-effects of Rb1, Rg1, Rg3-R, Rg3-S, and the Rg5 and Rk mixture were compared with those of a well-known active anxiolytic drug (diazepam). The oral administration of ginsenoside Rb1 significantly increased the number of open arm entries and the time spent on the open arm compared with those in the vehicle-treated group. Ginsenoside Rg1 and the Rg5 and Rk mixture also significantly increased the number of open arm entries and the time spent on the open arm. However, ginsenosides Rg3-R and Rg3-S did not increase the number of open arm entries or the time spent on the open arm. On the other hand, ginsenoside Rb1 and the Rg5 and Rk mixture decreased locomotor activity in a manner similar to diazepam. These data indicate that ginsenosides Rb1, Rg1, and the Rg5 and Rk mixture have anxiolytic-like effects, but ginsenosides Rg3-R and Rg3-S do not in this model. We provide evidence that some ginsenosides may be useful for the treatment of anxiety.

Animals↗

The pattern of action of blended Chinese traditional medicines to glucose tolerance curves in genetically diabetic KK-CAy mice.

The effects of blended Chinese traditional medicines applied for diabetes mellitus were studied on the pattern of action to the glucose tolerance curves in genetically diabetic KK-CAy mice. The glucose tolerance curves of KK-CAy mice (humping curve) were analyzed pharmacokinetically by the mathematical model (COmpartment-H model). The curves could be classified into several types of pattern through the analysis for the humping effect. Daisaikoto-Ka-Jio and Byakko-Ka-Ninjinto reduced the humping effect, whereas Hachimigan had a tendency to enhance it. On the combined effect of crude drugs prescribed in the blended medicines, the effect of Daisaikoto was lessened by subtracting Rehmanniae Rhizoma from Daisaikoto-Ka-Jio and Byakkoto (subtracted Ginseng Radix from Byakko-Ka-Ninjinto) had no inhibitory effect on the humping. Rehmanniae Rhizoma or Ginseng Radix along had the similar effect on decreasing the humping. the hypoglycemic component of Ginseng Radix (DPG3-2) decreased the humping effect in a dose-dependent manner. In conclusion, the effects of crude drugs and the active component of the crude drug supported those of the blended medicines on the humping effect by utilizing the pharmacolinetical analysis.

Animals↗

Saponins of plants of Panax species collected in Central Nepal, and their chemotaxonomical significance. III.

Panax pseudo-ginseng subsp. pseudo-ginseng has a carrot like root with a small rhizome. It was shown that the saponin composition of roots and rhizomes of this subspecies collected in Tibet and China was extremely poor. From the roots and rhizomes collected in Central Nepal, (specimen-PNct), only a small amount of an oleanolic acid saponin, beta-D-glucopyranosyl-oleanolate (2) was isolated together with a polyacetylene-alcohol, panaxynol (3). In another specimen (specimen-PNs), also collected in Central Nepal, two oleanolic acid saponins, stipleanoside R2 (4) and chikusetsusaponin IV (5) were detected. No dammarane saponin was identified in either specimen. P. pseudo-ginseng subsp. himalaicus (Subsp-H) has a big rhizome with a small round root. From rhizomes and roots of this subsp. collected in Central Nepal (specimen-HNct), a fairly large amount of dammarane saponins, ginsenosides-Rb1 (6), -Rd (7), -Re (9) and -Rg1 (10), gypenoside XVII (8), notoginsenoside-R1 (11), majonoside-R2 (12) and pseudo-ginsenoside-F11 (13) were isolated, while no oleanane saponin (oleanolic acid saponin) was identified in this subsp. Based on the present and previous studies, medicinal evaluation and chemogeographical correlation of Himalayan Panax spp. are discussed.

Chromatography, High Pressure Liquid↗

Determination of polyacetylenes and ginsenosides in Panax species using high performance liquid chromatography.

A new HPLC method was developed to separate and identify three polyacetylenes (panaxynol, panaxydol and 1,8-heptadecadiene-4,6-diyne-3,10-diol) found in Panax species. The mobile phase was a linear gradient of 2 : 1 : 3 to 2 : 1 : 1 (v/v/v) methanol/acetonitrile/water in 40 min. HPLC analysis was performed at a flow rate of 1.5 ml/min with UV detection at 254 nm. The contents of the polyacetylenes and ginsenosides in Panax ginseng (white ginseng and red ginseng), P. quinquefolium, P. japonicus, and P. noteginseng were determined using these methods. The species containing the highest polyacetylene content (0.080%) was P. quinquefolium cultivated in Nagano, Japan. Meanwhile, the species with the highest ginsenoside content (9.176%) was P. noteginseng cultivated in Yunnan, China.

Acetylene↗

Interactions between herbal medicines and prescribed drugs: a systematic review.

Despite the widespread use of herbal medicines, documented herb-drug interactions are sparse. We have reviewed the literature to determine the possible interactions between the seven top-selling herbal medicines (ginkgo, St John's wort, ginseng, garlic, echinacea, saw palmetto and kava) and prescribed drugs. Literature searches were performed using the following databases: Medline (via Pubmed), Cochrane Library, Embase and phytobase (all from their inception to July 2000). All data relating to herb-drug interactions were included regardless of whether they were based on case reports, case series, clinical trials or other types of investigation in humans. In vitro experiments were excluded. Data were extracted by the first author and validated by the second author. 41 case reports or case series and 17 clinical trials were identified. The results indicate that St John's wort (Hypericum perforatum) lowers blood concentrations of cyclosporin, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline; furthermore it causes intermenstrual bleeding, delirium or mild serotonin syndrome, respectively, when used concomitantly with oral contraceptives (ethinylestradiol/desogestrel), loperamide or selective serotonin-reuptake inhibitors (sertaline, paroxetine, nefazodone). Ginkgo (Ginkgo biloba) interactions include bleeding when combined with warfarin, raised blood pressure when combined with a thiazide diuretic and coma when combined with trazodone. Ginseng (Panax ginseng) lowers blood concentrations of alcohol and warfarin, and induces mania if used concomitantly with phenelzine. Garlic (Allium sativum) changes pharmacokinetic variables of paracetamol, decreases blood concentrations of warfarin and produces hypoglycaemia when taken with chlorpropamide. Kava (Piper methysticum) increases 'off' periods in Parkinson patients taking levodopa and can cause a semicomatose state when given concomitantly with alprazolam. No interactions were found for echinacea (Echinacea angustifolia, E. purpurea, E. pallida) and saw palmetto (Serenoa repens). In conclusion, interactions between herbal medicines and synthetic drugs exist and can have serious clinical consequences. Healthcare professionals should ask their patients about the use of herbal products and consider the possibility of herb-drug interactions.

Drug Interactions↗

A delivery circuit for normothermic reperfusion model.

In order to facilitate the introduction and assessment of Injectio Radix Ginseng Compositae in normothermic reperfusion model, a simplified delivery circuit is described herein. The circuit added mainly a venous reservoir collecting Injectio Radix Ginseng Compositae with cardiopulmonary bypass. Injectio Radix Ginseng Compositae was pumped into the ascending aorta of the animal after mixing with cardioplegia in the venous reservoir. The circuit was acceptable in terms of price by most inland medical laboratories. Perfusion as well as biochemical results monitored were satisfactory. Significant difference was noted between the average damage rates of the reperfused myocardial mitochondria in groups by ultrastructural analysis (70.12 +/- 2.56% vs. 25.33 +/- 17.62%, p = 0.023). No complications associated with perfusion technique occurred in either group. The circuit could offer a constant arterial perfusion, and was proved to be simple, safe and effective in cohort.

Animals↗

The herbal medicine Dai-Kenchu-Tou stimulates upper gut motility through cholinergic and 5-hydroxytryptamine 3 receptors in conscious dogs.

BACKGROUND: The herbal medicine Dai-Kenchu-To, composed of zanthoxylum fruit, ginseng root, and dried ginger rhizome, is clinically effective for uncomplicated postoperative adhesive intestinal obstruction. We investigated the effect of Dai-Kenchu-To and each ingredient on upper gastrointestinal motility and its mechanism of action. METHODS: Five mongrel dogs were equipped with 4-strain gauge-force transducers on the gastric body, antrum, duodenum, and jejunum to measure contractile activity of the circular muscle. Dai-Kenchu-To (1.5 g) or the separate ingredients zanthoxylum fruit, ginseng root, or dried ginger rhizome (1.0 g each) were administered by bolus into the gastric lumen. The effect of atropine, hexamethonium, phentolamine, propranolol, and ondansetron on intragastric Dai-Kenchu-To-induced contractions was studied. RESULTS: Intragastric Dai-Kenchu-To induced phasic contractions in the antrum, duodenum, and jejunum. Zanthoxylum fruit elicited phasic contractions mainly in the duodenum and jejunum, whereas dried ginger rhizome induced phasic contractions in the antrum. Ginseng root had no effect. Phasic contractions induced by intragastric Dai-Kenchu-To were inhibited by atropine and hexamethonium at all sites, although ondansetron inhibited these contractions in the antrum and duodenum. CONCLUSIONS: Intragastric Dai-Kenchu-To stimulates upper gastrointestinal motility through cholinergic and 5-hydroxytryptamine 3 receptors.

Animals↗

[Changes in productivity of plant cells as result of cultivation under the space flight conditions].

Effects of space flight on growth and biosynthetic features of plant cells were studied in two strains of ginseng (Panax ginseng) differing in growth and particularly biosynthetic activities, a strain of Lithospermum Erythrorhizon and a strain of Macrotomia Euchroma which produce biologically active naphroquin-derived pigments. --and also differ in growth and biosynthetic properties. Following exposure aboard MIR and a Space shuttle, cells of the callosal cultures were subjected to callosal or suspension passaging. Biomass yield and biologically active substances--ginseng saponins ginsenoids and shikonin were determined in the cells cultures. There was no evidence for the biomass yield to be significantly altered by space flight; however, the content of biologically active substances was materially changed with the strain.

Extraterrestrial Environment↗

Effects of crude drugs on glucose uptake in 3T3-L1 adipocytes.

In this study, various water-extracted crude drugs from Radix Asparagi, Radix Ginseng, Radix Scutellariae, Cortex Lycii Radicis, Cortex Phellodendri and Radix Ophiopogonis were investigated in their effects on [3H]-2-deoxyglucose uptake in 3T3-L1 adipocytes. Following treatment of cells with various crude drugs for 60 mim, the basal [3H]-2-deoxyglucose uptake in cultured 3T3-L1 cells was changed by Radix Asparagi from 140 pmole/min/mg protein of control to 513 (0.1 mg/ml), 201 (1 mg/ml) and 97 (10 mg/ml). Glucose uptake was changed to 324 (0.1 mg/ml), 146 (1 mg/ml) and 46 (10 mg/ml) with Radix Ginseng. In the presence of Radix Scutellariae, glucose uptake was changed to 215 (0.1 mg/ml), 213 (1 mg/ml) and 34 (10 mg/ml). In the presence of Cortex Lycii Radicis, glucose uptake was 230 (0.1 mg/ml), 188 (1 mg/ml) and 38 (10 mg/ml). In the case of Cortex Phellodendri and Radix Ophiopogonis, uptake was changed to 142 (0.1 mg/ml), 132 (1 mg/ml), 24 (10 mg/ml) and 489 (0.1 mg/ml), 374 (1 mg/ml), 344 (10 mg/ml), respectively. In insulin-stimulated cells, the [3H]-2-deoxyglucose uptake was changed by Radix Asparagi from 570 pmole/min/mg protein of the control to 816 (0.1 mg/ml), 674 (1 mg/ml) and 532 (10 mg/ml). After incubation with Radix Ginseng, the glucose uptake was changed to 254 (0.1 mg/mi), 123 (1 mg/mi) to 76 (10 mg/mi). In the presence of Radix Scutellariae, the glucose uptake was changed to 315 (0.1 mg/ml), 265 (1 mg/ml) and 33 (10 mg/ml). After incubation of Cortex Lycii Radicis, the uptake activity was changed to 281 (0.1 mg/ml), 248 (1 mg/ml) and 37 (10 mg/ml). In the case of Cortex Phellodendri and Radix Ophiopogonis, the activity of glucose uptake was measured as 747 (0.1 mg/ml), 523 (1 mg/ml), 33 (10 mg/ml) and 753 (0.1 mg/ml), 740 (1 mg/ml), and 421 (10 mg/ml), respectively. These results indicate that the water-extracted materials of Radix Asparagi and Radix Ophiopogonis increase the glucose uptake in basal and insulin-stimulated 3T3-L1 adipocytes.

3T3 Cells↗

In vitro immunomodulatory effects of herbal products.

Immunosuppressive drugs have been developed from natural products such as soil and fungi, which are also the sources of some commonly used herbal products. However, the effect of herbal products on immune response has not been investigated. Because these products can affect the host immune system they can induce either rejection or tolerance after a transplant procedure. To investigate the effects of ten commonly used herbal products on transplant-related immune function we performed in vitro lymphocyte proliferation tests using phytohemagglutinin, mixed lymphocyte culture (MLC) assay, and interleukin (IL)-2 and IL-10 production from MLC. Dong quai, ginseng, and milk thistle had nonspecific immunostimulatory effects on lymphocyte proliferation, whereas ginger and green tea had immunosuppressive effects. Dong quai and milk thistle increased alloresponsiveness in MLC, whereas ginger and tea decreased these responses. The immunostimulatory effects of dong quai and milk thistle were consistently seen in both cell-mediated immune response and nonspecific lymphoproliferation, whereas that of ginseng was not. The immunosuppressive effect of green tea and ginger were mediated through a decrease in IL-2 production, but the immunostimulatory effects of dong quai and milk thistle were not. We conclude that green tea, dong quai, ginseng, milk thistle, and ginger have effects on in vitro immune assays that may be relevant in transplantation in humans.

Angelica sinensis↗

[Effects of Ginsenosides Rg1 and Rb1 on Proliferation of Human Marrow Granulocyte-Macrophage Progenitor Cells]

Ginseng is a traditional Chinese medicine which has been used in treating anemia for thousands of years. It is composed of a lot of components. The main component is total saponin of panax ginseng (TSPG), which contains more than 20 ginsenosides including Rg1, Rb1 and so on. Previous studies have reported that total saponin of panax ginseng could promote hematopoiesis by stimulating proliferation of human erythroid grogenitor cells CFU-E and BFU-E, however, it had different effects on CFU-GM reported by various laboratories. In this study, CFU-GM assay was adopted to observe the ginsenosides Rg1 and Rb1's effects on the proliferation of human marrow grannulocyte-macrophage progenitor cells. The results showed that Rg1 and Rb1 had obvious promotive effect on the proliferation of CFU-GM, and the increasing rates of colony formation were up to (70.6 +/- 6.8)% and (65.1 +/- 6.3)%, respectively. There was no inhibiting effect on CFU-GM in high concentrations of Rg1 and Rb1. It is suggested that Rg1 and Rb1 can stimulate the proliferation of human granulocyte-macrophage progentors. The results of TSPG's various effects on CFU-GM might be caused by different contents of ginsenosides in TSPG used in different laboratories.

Journal Article↗

An overview of herbal supplement utilization with particular emphasis on possible interactions with dental drugs and oral manifestations.

Herbal medication in the United States is a popular form of therapy. This paper provides an overview of the utilization of herbal supplements with particular emphasis on possible interactions with oral health drugs and oral manifestations. Herbal supplements are regulated by the Dietary Supplement Health and Education Act (DSHEA), which limits their regulation by the U.S Food and Drug Administration (FDA). A number of studies indicate that there is a progressive increase in the utilization of herbal supplements. The majority of consumers of these products are white, middle-aged women who have some college education. Many of the consumers use pharmaceutical drugs concurrently, but most do not inform their health-care providers about their use of herbal supplements. Various herbal supplements have been reported or are suspected to interact with certain oral health drugs, the most important one being 1) bromelain, cayenne, chamomile, feverfew, dong quai, eleuthro/Seberian ginseng, garlic, ginkgo, ginger, ginseng and licorice interacting with aspirin; 2) aloe latex, ephedra, ginseng, rhubarb, cascara sagrada, licorice, and senna interacting with corticosteriods; 3) kava, St. John's wort, chamomile, and valerian interacting with central nervous system (CNS) depressant drugs; and 4) herbs acting on the gastrointestinal system, altering the absorption of several orally administered drugs. Further, the use of some herbal supplements has been reported to be associated with oral manifestations, including aphthous ulcers, lip and tongue irritation, and swelling with feverfew; gingival bleeding with feverfew and ginkgo; tongue numbness with echinacea; xerostomia with St. John's wort; oral and lingual dyskinesia with kava; and salivation with yohimbe. These potential effects of herbal supplements in conjunction with factors related to regulation restrictions suggest that the use of these products may be associated with various adverse reactions that can affect oral health and treatment. Dental hygienists should inform themselves about herbal supplements in order to offer appropriate oral health care to individuals who take these substances.

Blood Coagulation↗

Hemorrheological and circulatory effects of Gincosan.

Gincosan is a combined preparation containing 60 mg ginkgo biloba and 100 mg ginseng, standardized of 24% ginkgo flavone glycosides and 4% ginsenosides. Hemorrheological and circulatory effect as well as blood pressure behavior after the administration of gincosan were studied in an acute trial on 10 voluntary subjects with a mean age of 26 years. Systolic blood pressure decreased significantly both for the large-dose (120 mg ginkgo biloba +200 mg ginseng) and low-dose administration (60 mg ginkgo biloba +100 mg ginseng). Diastolic blood pressure and heart rate decreased only in the high dosage group. The pathologically increased spontaneous platelet aggregation is reduced by both dosages. Erythrocyte velocity in nail fold capillaries increased significantly only in the high dosage group. The parallel group comparison of the high dosage and placebo group showed that they differ only significantly concerning the erythrocyte rigidity, erythrocyte velocity in nail fold capillaries and spontaneous platelet aggregation. A trend towards a decrease in the systolic blood pressure is revealed (p less than 0.1).

Adult↗

[Determination of ginsenoside compound-K by reversed-phase high performance liquid chromatography].

Ginsenoside compound-K content in ginseng is very low, while it is the main intestinal bacterial metabolite and the final absorption style of the major components, such as ginsenosides Rbl and Rb2. The determination of ginsenoside compound-K in the fermentation liquor of ginseng saponins by reversed-phase high performance liquid chromatography was established. The separation was carried out under the following conditions: a Waters Symmetry C18 column (4.6 mm i.d. x 150 mm, 5 microm) was used at 35 degrees C with acetonitrile-water (48:52, v/v) as mobile phase at a flow rate of 1 mL/min. UV detection wavelength was set at 203 nm. The experimental results showed a good linear relationship between the peak area and mass concentration for ginsenoside compound-K within the range of 0.05-0.8 g/L (r = 0.9998). The relative standard deviation of peak area (n = 6) was 2.20%. The lowest detection limit (S/N = 3) was 2.5 mg/L. The average recoveries (n = 3) for the culture broth of ginseng saponins and notoginseng saponins were 98.6% and 99.7%, respectively. The method is rapid, simple, accurate and reproducible and can be utilized for the research and development of ginsenoside compound-K in pharmaceutical industry.

Chromatography, High Pressure Liquid↗

[Effects of aging and ginsenoside on atrial natriuretic peptide gene expression].

We investigated the levels of atrial natriuretic peptide (r-ANP) gene expression in the atria of rats aged 2-3 months and 14-18 months. In the meantime, we studied the effects of ginsenosides on r-ANP gene expression by determining the content of ANP messenger ribonucleic acid (r-ANP-mRNA). Male and female rats were abdominally injected aqueous solution of ginsenoside (prepared from ginseng stems and leaves (G-SL) and ginseng roots (G-R) 50 mg/kg body weight, once a day, for 7 days. Atrial total RNA was extracted by cold phenol method. The specificity and relative contents of r-ANP-mRNA were determined by using Northern blot and Dot blot hybridization respectively with alpha-32P-labeled r-ANP-cDNA probe. The results showed that the r-ANF-mRNA levels in male and female rats at the age of 14-18 months were about 15% and 60% of those in male and female rats at the age of 2-3 months. G-SL and G-R increased r-ANP-mRNA contents in male rats at the age of 14-18 months by 1 fold and 1.7 folds respectively; whereas they decreased r-ANP-mRNA contents in male rats at the age of 2-3 months. No apparent effects of ginsenosides on ANP gene expression was observed in female rats. These results showed that ANP gene expression is more declined in elder rats and ginseng has certain effects in the aspect of heart endocrine to combat decrepitude.

Aging↗

Stimulation of sexual performance in male rats with the root extract of dinh lang (Policias fruticosum L.).

Ginseng (Panax ginseng C.A. Meyer) is probably the best known medicinal plant, the extract of which is used in the Far East as a traditional remedy. Dinh lang (Polycias fruticosum L.) root extract (DLRE) was found to have a pharmacological spectrum similar to Ginseng. Experimental and clinical studies have shown a wide range of pronounced stimulatory effects of DLRE which showed low toxicity. It increases mental and physical performance. This study is devoted to demonstrate the effect of DLRE on sexual performance of male rats. Different age-cohorts of Wistar male rats [6-8 months old (n = 204), 16-18-months old (n = 240) and 22-24 month old (n = 122)], were used for these experiments. The rats of each age cohort were divided into 4 groups. One group received saline, others were treated with various doses of DLRE daily. Treatment started 10 days before the screening test and continued during the test period. DLRE reduced the percentage of non-copulators in the aged rats compared to the younger ones. In the aged rats DLRE transformed high percentage of sluggish rats to sexually fully active animals. In sexually fully active 6-8 months old rats the percentage of rats displaying ejaculation with the second female was found to be significantly higher in DLRE-treated males. Also the recovery of the sexually exhausted male rats proved to be faster in DLRE-treated groups.

Aging↗