Anticancer properties and pharmaceutical applications of ginsenoside compound K: A review.

Ginsenoside compound K (CK) is the major intestinal bacterial metabolite of ginsenosides that exhibits anticancer potential in various cancer cells both in vitro and in vivo. The anticancer types, mechanisms, and effects of CK in the past decade have been summarized in this review. Briefly, CK exerts anticancer effects via multiple molecular mechanisms, including the inhibition of proliferation, invasion, and migration, the induction of apoptosis and autophagy, and anti-angiogenesis. Some signaling pathways play a significant role in related processes, such as PI3K/Akt/mTOR, JNK/MAPK pathway, and reactive oxygen species (ROS). Moreover, the effects of CK combined with nanocarriers for anticancer efficiency are discussed in this review. Furthermore, we aimed to review the research progress of CK against cancer in the past decade, which might provide theoretical support and effective reference for further research on the medicinal value of small molecules, such as CK.

Prevalence of the methylenetetrahydrofolate reductase 677C>T polymorphism in the pregnant women of Yunnan Province, China.

Mutations in the methylenetetrahydrofolate reductase (MTHFR) gene can result in a reduced ability to utilize folic acid. The MTHFR 677C>T polymorphism in particular has been linked to both birth defects and pregnancy-associated diseases. This study aimed to evaluate the prevalence of the MTHFR 677C>T mutation among pregnant women in Yunnan Province so as to collect baseline data that may be utilized to guide folic acid supplementation efforts and to support related disease prevention programs. We retrospectively reviewed 3387 pregnant women from Yunnan Province. The MTHFR 677C>T polymorphism was identified using polymerase chain reaction (PCR) and DNA sequencing. In total, 1350 (39.9%) subjects were homozygous for the C allele (CC), 1540 (45.4%) subjects were heterozygous (CT), and 497 (14.7%) subjects were homozygous for the T allele (TT). The MTHFR 677C>T polymorphism was found to be present within the studied population, with ∼60% of these patients being either heterozygous or homozygous for the mutant allele and with an overall T allele frequency of 0.37. The frequency of the T allele was significantly higher among pregnant women with complications relative to women with healthy pregnancies, particularly among women <30 years old. As such, the maternal MTHFR 677C>T polymorphism may be a genetic risk factor associated with pregnancy complications and may help identify pregnant women at a high risk of such complications.

Compound K induces neurogenesis of neural stem cells in thrombin induced nerve injury through LXRα signaling in mice.

Intracerebral hemorrhage (ICH) causes neurological function deficit due to the loss of neurons surrounding the hematoma. Increased neurogenesis of endogenous neural stem cells (EnNSCs) is believed to increase cell proliferation and differentiation, thereby improving the neurological deficit. However, there are still limited drugs that are effective for treating neurological deficit. So, the effects of compound K (CK) in EnNSCs were measured after thrombin-induced mice models both in vivo and in vitro, and investigated the probable mechanisms of CK during pro-neurogenesis. The results revealed that 10 µM CK promotes neurogenesis, proliferation and reduces apoptosis of EnNSCs after induction by thrombin. After that, CK treatment increased the neurogenesis of EnNSCs through liver X receptor α (LXRα) signaling pathway using adeno-associated virus knockdown and knocked out mice of LXRα gene. Finally, intraperitoneal injection of 10 mg/kg CK improved the neurogenesis of subventricular zone (SVZ), myelin repair and behavioral deficit after stereotaxic injection of thrombin in the basal ganglia of mice, and this process involved LXRα. These observations provided evidence regarding the effect of CK in pro-neurogenesis via LXRα activation, and suggested further evaluation of it due to its potential role as an effective modulator in the treatment of ICH.

Effects of long-term rapamycin treatment on glial scar formation after cryogenic traumatic brain injury in mice.

Glial scar impedes axon regeneration and functional recovery following traumatic brain injury (TBI). Although it has been shown that rapamycin (a specific inhibitor of mammalian target of rapamycin) can reduce astrocyte reactivation in the early stage of TBI, its effect on glial scar formation has not been characterized in TBI and other acute brain injury models. To test this, ICR mice received daily administration of rapamycin (0.5 or 1.5 mg/kg, i.p.) beginning at 1 h after cryogenic TBI (cTBI). The results showed that at 3 d post-injury, 1.5 mg/kg rapamycin increased cTBI-induced motor functional deficits and infarct size, and attenuated astrocyte reactivation in the ipsilateral cortex, while 0.5 mg/kg rapamycin did not worsen brain damage and only slightly attenuated astrocyte reactivation. Furthermore, at 7 and 14 d after cTBI, 0.5 mg/kg rapamycin group showed a better motor functional performance than cTBI group. At 14 d post-injury, 0.5 mg/kg rapamycin significantly reduced the area and thickness of glial scar and chondroitin sulfate proteoglycan expression, accompanied by decreased expression of p-S6 and enhanced expression of growth associated protein 43 (an axon regeneration marker) in the region of glial scar. Our data suggest that long-term treatment with rapamycin can inhibit glial scar formation after cTBI, which may be involved in the mechanisms of increased axon regeneration and improved neurological functional recovery, and low-dose rapamycin may be more beneficial for such a therapy.

[Effects of PKCα/c-fos, Bax/Bcl-2 expression on the proliferation and apoptosis of rat pulmonary arterial smooth muscle cells in hypoxia].

OBJECTIVE: To explore the effects of PKCα/c-fos, Bax/Bcl-2 on the proliferation and apoptosis of rat pulmonary arterial smooth musclecells(PASMCs) in hypoxia. METHODS: The PASMCs of rats had been isolated and cultured, and then were cultured under normoxia (5%CO2、21%O2、74%N2)and hypoxia(5%CO2,2% O2,93%N2)condition for 24 h and 48 h, respectively. The proliferation of PASMCs was tested by methylthiazolyltetrazolium (MTT). The changes of PASMCs apoptosis were detected by Annexin V-FITC/PI staining combined flow cytometry. RT-PCR and Western blot analysis were performed to detect the gene and protein levels of PKCα/c-fos, Bax/Bcl-2, respectively. All experiments were repeated three times with at least triplicate samples. RESULTS: The proliferation of PASMCs in hypoxia group were stronger than that of normoxia group after 24 h and 48 h (P < 0.01), while the apoptosis rate did not change significantly. Meanwhile, the higher levels of PKCα, c-fos, Bcl-2 mRNA and proteins after hypoxia for 24 h and 48 h were detected by RT-PCR and Western blot analysis, while the ex-pression levels of Bax had no significant difference under normoxic and hypoxic conditions. CONCLUSIONS: Elevated proliferation and expression of PKCα, c-fos, Bcl-2 was observed in rat PASMCs in hypoxia, and while the apoptosis rate had no significant change.

[The comparison study on effects of water-soluble components of fine particulate matter on vasomotor functions in aortas from rats after exposure in different time].

OBJECTIVE: To compare the difference of vasomotor functions in aortas segments from Wistar rats between 1-hour and 6-hours after exposure of water-soluble components of fine particulate matter (PM2.5). METHODS: All 30 Wistar rats were assigned to five groups (n=6 for each group) at random: the blank control group, control group for 1-hour and 6-hours, exposure group for 1-hour and 6-hours. The rats were sacrificed 1-hour or 6-hours later and aorta ring segments were mounted on wire myographs. RESULTS: (1) There was no significant difference in vasomotor functions among three control groups (P>0.05). (2) 1-hour or 6-hours after exposure there was a decrease of contraction elicited by 60 mmol/L KCl in contrast to the control group (P<0.05), whereas no significant change between the exposure group for 1-hour and 6-hours (P>0.05). (3) On the level of 10(-5) or 10(-7) mol/L, 1-hour after exposure there was a decrease in endothelium-dependent acetylcholine (ACh) elicited relaxation precontracted by 10(-6) mol/L NE compared with the control group (P<0.01 or P<0.05), on the level from 10(-5) to 10(-7) mol/L there was a decrease compared with the exposure group for 6-hours (P<0.05), whereas no difference between the exposure group for 6-hours and the control group (P>0.05). On the level from 10(-5) to 10(-9) mol/L, 1-hour after exposure there was a decrease in endothelium-independent sodium nitroprusside (SNP) elicited relaxation precontracted by 10(-6) mol/L NE as compared with the control group (P<0.01 or P<0.05) and a decrease on the level of 10(-6) or 10(-9) mol/L compared with the exposure group for 6-hours (P<0.05), 6-hours after exposure a decrease was caused as compared with the control group on the level from 10(-5) to 10(-7) mol/L (P<0.01 or P<0.05). CONCLUSIONS: Inhibition of contraction and impairment of relaxation in aortas should be caused 1-hour after exposure to water-soluble components of PM2.5 in the air, which is weaken 6-hours after exposure.

Vasorelaxant effect of taurine is diminished by tetraethylammonium in rat isolated arteries.

Although the vasorelaxant effects of taurine have been studied in rabbit ear artery, rat isolated aorta and mesenteric artery, its pharmacological properties in other vascular beds and underlying mechanism(s) are still not well clarified. The present study was designed to observe the effects of taurine on the contractions induced by depolarization and phenylephrine in rat isolated aortic, renal and mesenteric arterial rings, and to get an insight into its mechanism(s). Arterial rings were suspended in organ baths and tension was recorded isometrically. Taurine 20-80 mM produced concentration-dependent relaxations of rat isolated aortic rings precontracted by 30 mM potassium chloride and 1 microM phenylephrine; the maximal relaxation was 17.17+/-3.18% and 22.23+/-1.83% respectively. The relaxation was not affected by 0.1 mM NG-nitro-L-arginine methylester ester (a nitric oxide synthetase inhibitor), 10 microM indomethacin (a cyclooxygenase inhibitor), 1 mM 4-aminopyridine (a K(V) blocker), 10 muM glibenclamide (a K(ATP) blocker), 1 mM barium chloride (BaCl(2), a K(IR) blocker), and 100 nM iberiotoxin (a BK(Ca) blocker), but was nearly abolished by 10 mM tetraethylammonium (TEA, a non-selective potassium channel blocker). Preincubation with taurine 20-60 mM did not affect the basal tone but inhibited the contraction induced by phenylephrine, and the inhibitory effect was attenuated by TEA in isolated renal and mesenteric arterial rings. Present experiments show that taurine relaxes contracted rat aorta and inhibits the phenylephrine-induced contraction of renal and mesenteric arteries, and suggest that a mechanism related to potassium channel opening may be involved in the action of taurine.

[Effects of electromagnetic pulse on contents of amino acids in hippocampus of rats].

OBJECTIVE: To investigate the relationship between the changes of amino acids contents in hippocampus of rats and electromagnetic pulse (EMP) exposure. METHODS: Rats were decapitated and hippocampus were removed after EMP (6 x 10(4) V/m, rise time 20 ns, pulse width 30 micro s, 5 pulses in 2 minutes) irradiation, and contents of amino acids were detected with high performance liquid chromatograpy (HPLC). RESULTS: The contents of aspartic acid (Asp) and glutamic acid (Glu) increased significantly 0, 3, 6 h after irradiation. The peak values of Asp [(17.25 +/- 1.63) pmol/ micro l] and Glu [(13.67 +/- 0.95) pmol/ micro l] were higher than those of control [(10.56 +/- 1.50), (6.94 +/- 1.10) pmol/ micro l respectively, P < 0.05]. Then both decreased gradually and reached the normal level 24 - 48 h after irradiation. The contents of glycine (Gly), taurine (Tau) and gamma-aminobutyric acid (GABA) also rose after exposure, the peak value of them [(4.51 +/- 0.60), (29.85 +/- 2.70), (5.14 +/- 0.73) pmol/ micro l respectively] were higher than those of control group [(2.18 +/- 0.31), (9.88 +/- 1.47), (2.84 +/- 0.67) pmol/ micro l, P < 0.05], then recovered 48 h after irradiation. The value of Glu/GABA increased immediately after exposure (3.45 +/- 0.25, P < 0.05), then decreased 24 h (1.62 +/- 0.23, P < 0.05) and recovered 48 h after exposure. CONCLUSION: The toxic effect of excess excitatory amino acids may be partly responsible for the early retardation (within 24 h) of learning of rats.