The ginseng's fireness is associated with the lowering activity of liver Na(+)-K(+)-ATPase.
BACKGROUND
Ginseng is an herbal medicine used worldwide that possesses a wide range of pharmacological activities. However, its side effects are rarely discussed. The experience of Chinese medicine has revealed that taking ginseng at a high dose chronically can cause fireness, i.e., the ginseng-abuse syndrome. Here, we explored the mechanism of ginseng's fireness by comparing the energy metabolism of mice affected by red ginseng (RG), ginseng (GS), ginseng leaves (GL) and American ginseng (AG), which exhibit different drug properties according to the theory of TCM.


METHODS
KM mice were randomly divided into five groups (n≥30 per group) and administered distilled water or drugs, respectively. Mice receiving RG, GS, or GL received 4.5g/(kgday), while the mice receiving AG received 3g/(kgday). Control mice received distilled water. The duration of exposure for all groups was 31 days. The mice's physical characteristics, such as eye condition, rectal temperature, saliva secretion, urine, stool weight, blood coagulation time and swimming time, were measured at different times after administration. Energy metabolism indexes were measured via TSE phenoMaster/LabMaster animal monitoring system, including the mice' 24h oxygen consumption (VO2), carbon dioxide production (VCO2), heat production (H) and energy expenditure (EE). Biochemical indices were measured by ultraviolet spectrophotometer and microplate reader, including pyruvic acid content in serum and succinate dehydrogenase (SDH) activity, lactate dehydrogenase (LDH) activity, the Na(+)-K(+)-ATPase activity and the content of glycogen in the liver tissue.


RESULTS
After 31 days of drug administration, mice in the RG and GS groups exhibited obviously more eye secretions, less saliva secretion and less urine. Compared with the control group, the swimming times of mice in the GS, AG and GL groups were significantly prolonged; the clotting time of mice in the GL was extended significantly; VCO2, H and EE of mice in the GS group were obviously increased; Pyruvate content of mice in the RG group showed an initial decrease followed by an increase; SDH activity of mice in the AG and GL groups was significantly inhibited; LDH activity of the mice showed no significant difference among different groups; Na(+)-K(+)-ATP enzyme activity of the RG and GS groups showed up-regulation initially and then down-regulation; the content of hepatic glycogen of mice in the GS and GL groups increased significantly.


CONCLUSIONS
The results demonstrated that RG and GS with their warm drug nature could enhance the body's energy metabolism to produce their dryness to the body. The liver Na(+)-K(+)-ATP enzyme activity may be the primary index for indicating the fireness of ginseng. In addition, our results demonstrated that ginseng, especially red ginseng, is not suitable for long time application with a higher dose.
College of Pharmacy, Liaoning University of Traditional Chinese Medicine, 77 Life one Road, DD Port, Dalian 116600, PR China. Electronic address: yuebaiangel9@163.com.
Xu
X
Xu
College of Pharmacy, Liaoning University of Traditional Chinese Medicine, 77 Life one Road, DD Port, Dalian 116600, PR China. Electronic address: deqiangdou@126.com.
Deqiang
D
Dou
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D015352:Dry Eye Syndromes / Q000139:chemically induced / Q000503:physiopathology; D004734:Energy Metabolism / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000633:toxicity*; D005123:Eye / Q000187:drug effects / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D005894:Panax / Q000737:chemistry* / Q000145:classification; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000633:toxicity*; D018515:Plant Leaves / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal; D019289:Pyruvic Acid / Q000097:blood; D012472:Salivation / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism; D022722:Thermogenesis / Q000187:drug effects; D013997:Time Factors; D014554:Urination / Q000187:drug effects
D004791:Enzyme Inhibitors; D010936:Plant Extracts; D002245:Carbon Dioxide; D019289:Pyruvic Acid; D006003:Glycogen; D007770:L-Lactate Dehydrogenase; D013385:Succinate Dehydrogenase; D000254:Sodium-Potassium-Exchanging ATPase
American ginseng; Chinese medicine property; Dryness; Energy metabolism; Ginseng; Ginsenoside f(4) (pubchem cid:102004835); Ginsenoside rb(1) (pubchem cid:432524); Ginsenoside re (pubchem cid:441921); Ginsenoside rg(1) (pubchem cid:441923); Ginsenoside rg(3) (pubchem cid:12901617); Ginsenoside rg(5) (pubchem cid:11550001); Ginsenoside rh(1) (pubchem cid:12855920); Ginsenoside rh(2) (pubchem cid:14081290)