An early study revealed that ginseng leaf extract caused CNS depression and neuroleptic effects in mice 303132. The extract-induced CNS depression was observed along with a reduction of spontaneous and exploratory movements and the potentiation of hypnotic actions of hexobarbital. Analgesic and anticonvulsant activities were also confirmed in this study. Moreover, ginseng leaf extract inhibited conditioned avoidance response in the pole climbing test.

Effects of saponins from Chinese ginseng leaf-stem on memory, learning and biogenic monoamines of the brain were also examined in rats 33. Results showed that ginseng root saponins improved learning and memory in normal male rats, while the effects of ginseng leaf-stem saponins on anti-electroconvulsive shock-induced impairment of memory consolidation were more intense. Both leaf-stem and root saponins raised the levels of biogenic monoamines significantly in the brains of normal rats. In another study, the effects of ginseng leaf-stem saponins on learning and memory of one-way avoidance were evaluated in shuttle-box rats 34. The data indicated that ginseng leaf-stem saponins facilitated the acquisition of learning and memory and ameliorated scopolamine and cycloheximide amnesia. Effects of ginseng leaf extract on the CNS were also examined in various species of ginseng 35. For example, Siberian ginseng leaf extract was found to have anti-fatigue, anti-stress and anti-depressive effects. An In vivo study revealed that a Chinese herbal formula consisting of ginseng leaf, namely Jiannaoning, improved memory function in rats with cerebral ischemia 36 and that Jiannaoning regulated the levels of interleukin-2, interleukin-6 and neuropeptide Y in rat brain. Moreover, ginsenosides from ginseng leaf-stem affected the level of glucocorticoid receptor (GR) in brain cytosol in heat-damaged rats 37. Binding activities of GR in brain, lung and liver cytosols and the expression levels of GR mRNA in brain and liver cytosols were all higher in the ginsenosides-treated groups than the untreated control group. Ginsenosides reduced GR binding activity in viscera which may have induced the expression of GR mRNA. Another study 38, however, indicated that extract from the aboveground part of Chinese ginseng (including ginseng leaf-stem) had a weaker effect or no effect on the animal behavior compared to ginseng root.

Ginseng leaf extracts had preservative effects on the cardiac and vascular systems and prevented myocardial ischemia in animal experiments 39. In anaesthetized open-chest dogs treated with American ginseng leaf extract, the myocardial infarct size, activity of serum creatine kinase (CK), lactate dehydrogenase (LDH), the contents of serum free fatty acid (FFA) and lactoperoxidase (LPO) significantly decreased, whereas the activity of serum superoxide dismutase (SOD) and Gtutathione peroxidase (GSH-Px) significantly increased. At the same time, myocardial blood flow was increased and coronary vascular resistance was decreased. The results indicate that the ginseng leaf extract protected against myocardial ischemia by modifying metabolic dysfunction of FFA, inhibiting oxygen free radical-mediated peroxidation of membrane lipids, enhancing endogenous antioxidase activity and increasing myocardial blood supply. Another study 40 confirmed that ginseng leaf-stem extract protects against acute myocardial infarction (AMI) in rats by promoting angiogenesis in the infracted or ischemic area of myocardium.

A previous study demonstrated that Chinese ginseng leaf-stem extracts had beneficial effects on the preservation of cardiac and coronary vascular functions after cold storage for 12 hours in isolated rat hearts. The extracts increased coronary artery dilation and coronary flow in response to an endothelial-dependent vasodilator (ACh), protected the coronary endothelium, prevented coronary vascular dysfunction induced by reperfusion injury after hypothermic heart preservation and attenuated reperfusion damage of vascular smooth muscle cells 41.

Furthermore, American ginseng leaf-stem saponins were reported to antagonize the effects of norepinephrine (NE), potassium chloride and calcium chloride on the isolated aortic strips of rabbits 42. The saponins inhibited intracellular and extracellular Ca²⁺-dependent contractions induced by NE in rabbit aortic strips. Another study revealed that American ginseng saponins inhibited the contractility of guinea pig papillary muscle 43. A randomized controlled trial with double blinding indicated that Shenshao Tongguan Piana, a proprietary Chinese medicine formula containing ginseng leaf-stem extract, effectively treated angina pectoris in coronary heart disease (CHD) with effective rates of 94.7% and 67.0% in the treatment and control groups respectively 44.

Several studies revealed that ginseng leaf-stem extract affected atrial natriuretic peptide (ANP) gene expression in older rats 4546 and that both ginseng leaf-stem and root extracts increased the ANP mRNA in rats. An in vivo study on American ginseng leaf extracts showed that the expression of vascular endothelial growth factor (VEGF) and mean micro-vessel density were higher in the ginseng leaf saponin groups than in the vehicle model group and that the expression of basic fibroblast growth factor (bFGF) was higher in the ginseng leaf saponin groups than in the vehicle model group 40, suggesting that ginseng leaf-stem extracts may protect myocardium from ischemic injury in rats with AMI by up-regulating VEGF and bFGF in myocardial cells thereby inducing angiogenesis.

Ginsenosides from Chinese ginseng leaf-stem significantly increased the protein and RNA contents of muscles and liver in rats and that ginsenosides accelerated the growth of young pigs. It was suggested that ginsenosides may have direct influence on RNA and protein synthesis 32.

Ginsenosides from ginseng leaf-stem coupled with aerobic exercise lowered serum lipid, regulated lipid metabolism, promoted antioxidation and enhanced immune activity 47. Oral administration of ginsenosides extracted from ginseng leaf-stem significantly inhibited the rise of total lipid, cholesterol and triglyceride in rabbits 48.

One third of diabetic patients use dietary supplements or alternative medicines 49. Previous studies indicated that ginseng is an important alternative medicine to treat diabetes and both Chinese and American ginseng roots had anti-hyperglycemic effect 50515253. Ginseng berry extract reduced hyperglycemia and body weight in C57BL/6J ob/ob mice 5455 and C57BL/Ks db/db mice 56. Ginseng leaf-stem extracts also had this anti-diabetic effect 215758. Ginseng leaf and root extracts increased the basal content and glucose-dependent secretion of insulin in blood 59.

Active ingredients and hypoglycemic properties of American ginseng leaf were examined with high performance liquid chromatography (HPLC) in diabetic ob/ob mice 21. The results indicated that American ginseng leaf extract significantly reduced blood glucose levels. Intraperitoneal glucose tolerance test showed that the leaf extract significantly improved glucose disposal. Thus, American ginseng leaf extract, with its high ginsenoside yield, may be an inexpensive alternative to the root for diabetic treatment. Similar anti-hyperglycemic activity was observed in a study on total ginsenosides of Chinese ginseng leaf-stem 60.

Obesity is a serious medical disorder that may cause a myriad of health problems, such as heart disease, hypertension and adult-onset diabetes. Berry, root and leaf extracts of American and Chinese ginseng as well as total ginsenosides of Chinese ginseng leaf-stem had anti-obesity activities in animals and that American ginseng leaf extract significantly reduced body weight in adult ob/ob mice 2154566061.

Anti-cancer effect of ginseng leaf-stem is an important pharmacological function. Anti-cancer effects of Chinese ginseng leaf extract were found after co-administration of acidic polysaccharide from Chinese ginseng leaf enhanced therapeutic effects and reduced hematopoietic complications induced by systemic chemotherapy or radiation therapy 62. Acidic polysaccharide may be a novel and potent immunotropic agent to improve cellular immunity and an anti-cancer drug to treat urological cancer patients. Extract of Indian ginseng leaf (Ashwagandha) had anti-cancer activities 63. Total saponins from Panax ginseng leaf-stem protected against cyclophosphamide (a commonly used anti-cancer compound)-induced genotoxicity and apopotosis in bone marrow cells and peripheral lymphocytes in mice 64. Thus, ginseng leaf extracts can be a new source for anti-cancer drugs.

Kitts et al. also confirmed that ginsenoside Rh2 extracted from American ginseng leaf induced cytotoxity in cultured leukemia THP-1 cells 65. Flow cytometry of cells stained with annexin V-fluorescein isothiocyanate and propidium iodide showed that the Rh2 from ginseng leaf significantly increased apoptosis at a concentration that inhibited cell viability by 50% (LC₅₀). Ginsenoside (Rh2) may be the active ingredient for anti-cancer activity in ginseng leaf 65.

Extracts from American ginseng root and berry possess antioxidant properties 513356667 and so does ginseng leaf extract. In streptozotocin-induced diabetic rats, oral administration of wild ginseng leaf extract (WGLE) effectively suppressed lipid peroxidationin diabetic rats 68. Similar antioxidant activities were observed in cultivated and wild Korean ginseng leaf extracts 69. It was confirmed that water, methanol and ethanol extracts form freeze-dried leaves of wild ginseng exhibited scavenging activities towards DPPH (2,2-diphenyl-2-picrylhydrazyl hydrate), superoxide anion and hydroxyl radicals. Among various solvent used to extract wild ginseng leaves, ethanol yielded the highest DPPH, hydroxyl radical scavenging and ferrous ion chelating activity 70.

Not surprisingly, the saponin extracted from American ginseng leaf-stem (0.25-1 mg/ml) also demonstrated antioxidant properties in cultured rat cardiomyocytes 5. Moreover, Rb1, Rb2 and Rb3 extracted from Panax ginseng leaf-stem restored the action potentials of free radical damaged cells 71.

Toxicity of ginsenosides from Panax ginseng leaf-stem was determined in mice. When mice were given ginsenosides per oral, no death occurred 3132. Another report 84 indicated that the LD₅₀ values of crude saponin fraction and saponins of ginseng leaves were 381 mg/kg and 299 mg/kg respectively.

Ginseng leaf-stem extracts did not affect the number of erythrocytes, leukocytes, thrombocytes, the amount of hemoglobin or renal function in subacute toxic experiments in rats 32. Body weight, food consumption and liver weight of rats increased 32. Brain, heart, lungs, liver, spleen, kidneys, stomach, testes and ovaries were normal on gross examination and histopathological study. These findings suggested that high quality ginseng leaf-stem and its preparations were safe in normal use.