A microscale 3D organ on a chip for recapitulating reciprocal neuroendocrine crosstalk between the hypothalamus and the pituitary gland.

Conventional 2D or even recently developed 3Din vitroculture models for hypothalamus and pituitary gland cannot successfully recapitulate reciprocal neuroendocrine communications between these two pivotal neuroendocrine tissues known to play an essential role in controlling the body's endocrine system, survival, and reproduction. In addition, most currentvitroculture models for neuroendocrine tissues fail to properly reflect their complex multicellular structure. In this context, we developed a novel microscale chip platform, termed the 'hypothalamic-pituitary (HP) axis-on-a-chip,' which integrates various cellular components of the hypothalamus and pituitary gland with biomaterials such as collagen and hyaluronic acid. We used non-toxic blood coagulation factors (fibrinogen and thrombin) as natural cross-linking agents to increase the mechanical strength of biomaterials without showing residual toxicity to overcome drawbacks of conventional chemical cross-linking agents. Furthermore, we identified and verified SERPINB2 as a reliable neuroendocrine toxic marker, with its expression significantly increased in both hypothalamus and pituitary gland cells following exposure to various types of toxins. Next, we introduced SERPINB2-fluorescence reporter system into loaded hypothalamic cells and pituitary gland cells within each chamber of the HP axis on a chip, respectively. By incorporating this SERPINB2 detection system into the loaded hypothalamic and pituitary gland cells within our chip platform, Our HP axis-on-chip platform can better mimic reciprocal neuroendocrine crosstalk between the hypothalamus and the pituitary gland in the brain microenvironments with improved efficiency in evaluating neuroendocrine toxicities of certain drug candidates.

Protective mechanisms of loquat leaf extract and ursolic acid against diabetic pro-inflammation.

The pharmacological effectiveness of loquat leaf extract (LE) and its important component, ursolic acid (UA), in the treatment of diabetes mellitus, has been well established in traditional medicine; however, the mechanism underlying their action is still unclear. We evaluated the protective effects of LE and UA against hyperglycemia-induced advanced glycation end product (AGE) formations and hepatic pro-inflammation. Oral administration of UA and LE at a dose of 50 mg/kg/day for 15 days yielded no significant hypoglycemic effect in diabetic db/db mice. UA and LE suppressed hepatic oxidative stress and AGE formation in diabetic mice, and this was followed by the downregulated mitogen-activated protein kinase signaling and nuclear factor κ B (NF-κB) activity. To identify the molecular target of LE and UA, a docking simulation was performed, and this predicted UA to bind to liver kinase B1 (LKB1), an upstream of AMP-activated protein kinase (AMPK)/transcription factor forkhead box O3 (FOXO3) axis. UA reversed the high-glucose-induced downregulation of LKB1-AMPK1-FOXO3 activation and antioxidant gene transcription. These findings demonstrated the antioxidant and anti-inflammatory effects of UA and LE against hyperglycemia-induced hepatic inflammation. Furthermore, we speculate that the LKB1/AMPK/FOXO3 pathway is a potential target responsible for these beneficial effects of LE and UA.

Caterpillar Medicinal Mushroom, Cordyceps militaris (Ascomycota), Attenuates Aß1-42-Induced Amyloidogenesis and Inflammatory Response by Suppressing Amyloid Precursor Protein Progression and p38 MAPK/JNK Activation.

The deposition of amyloid beta (Aß) is a neuropathological feature of Alzheimer's disease (AD). Cordyceps militaris is an edible medicinal fungus in Asian countries with antioxidative, antiaging, antitumor, and immunomodulatory effects. In this study, we investigated the neuroprotective mechanisms of C. militaris in the brain of Aß1-42-injected AD mice. An intracerebroventricular injection of Aß1-42 (total 3 µg/mouse) resulted in neurological damage, including amyloidogenesis and neuroinflammation; however, C. militaris attenuated Aß1-42-induced amyloidogenesis and inflammatory responses. Oral administration of C. militaris at concentrations of 100 and 200 mg/kg suppressed acetylcholinesterase activity. In addition, C. militaris treatment downregulated amyloid precursor protein levels, with a decrease in ß-secretase activity. Moreover, C. militaris significantly enhanced the expression of brain-derived neurotrophic factor. Furthermore, C. militaris-administered groups had inactivated inflammatory responses by downregulation of inducible nitric oxide synthase and cyclooxygenase-2 protein expression. The injection of Aß1-42 resulted in the activation of p38 MAPK and c-Jun N-terminal kinase, which was rescued by C. militaris. These results suggest that C. militaris has a protective effect against Aß1-42-induced neurological damage.

Therapeutic potential of Chinese prescription Kangen-karyu for patient with lifestyle-induced metabolic syndrome.

We report a case of a 65-year-old patient with hypertension, dyslipidemia, type 2 diabetes, chronic kidney disease, and hyperuricemia, who showed an improvement in lifestyle-induced metabolic syndrome on the administration of 7.5 g of Kangen-karyu extract per day for 6 months. The levels of serum total cholesterol, low-density lipoprotein-cholesterol, and triglycerides were decreased. The systolic/diastolic blood pressure was decreased following administration. Other parameters such as estimated glomerular filtration rate, creatinine, uric acid, aspartate transaminase, alanine aminotransferase, γ-glutamyl transpeptidase, and creatine phosphokinase were improved by the administration of Kangen-karyu extract. At that time, the physical and subjective symptoms had partially disappeared. We present evidence supporting the use of Kangen-karyu extract against metabolic syndrome.

Seomae mugwort and jaceosidin attenuate osteoarthritic cartilage damage by blocking IκB degradation in mice.

Seomae mugwort, a Korean native variety of Artemisia argyi, exhibits physiological effects against various diseases. However, its effects on osteoarthritis (OA) are unclear. In this study, a Seomae mugwort extract prevented cartilage destruction in an OA mouse model. In vitro and ex vivo analyses revealed that the extract suppressed MMP3, MMP13, ADAMTS4 and ADAMTS5 expression induced by IL-1ß, IL-6 and TNF-α and inhibited the loss of extracellular sulphated proteoglycans. In vivo analysis revealed that oral administration of the extract suppressed DMM-induced cartilage destruction. We identified jaceosidin in Seomae mugwort and showed that this compound decreased MMP3, MMP13, ADAMTS4 and ADAMTS5 expression levels, similar to the action of the Seomae mugwort extract in cultured chondrocytes. Interestingly, jaceosidin and eupatilin combined had similar effects to Seomae mugwort in the DMM-induced OA model. Induction of IκB degradation by IL-1ß was blocked by the extract and jaceosidin, whereas JNK phosphorylation was only suppressed by the extract. These results suggest that the Seomae mugwort extract and jaceosidin can attenuate cartilage destruction by suppressing MMPs, ADAMTS4/5 and the nuclear factor-κB signalling pathway by blocking IκB degradation. Thus, the findings support the potential application of Seomae mugwort, and particularly jaceosidin, as natural therapeutics for OA.

Therapeutic effect of Chinese prescription Kangen-karyu in patients with diabetic nephropathy.

Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. A number of new therapies have been developed based on the pathogenic factors of diabetic nephropathy such as intensive glycemic control, precise hypertension control, lifestyle modifications including exercise and an energy-restricted diet, and numerous novel agents. The utilization of traditional Chinese medicine for patients with diabetic nephropathy has also received increasing attention due to its wide availability, weak side-effects, and proven therapeutic mechanisms and benefits. In this paper, we report the case of patients with diabetic nephropathy, stage 2 or 3. Kangen-karyu extract (7.5 g/day) was administered three times per day for 6 months. The estimated glomerular filtration rate was increased at the 6-month follow-up. The serum creatinine level decreased following administration. At that time, somatic and subjective symptoms had partially disappeared. Here, we present evidence that Kangen-karyu exerts a renoprotective effect against the development of diabetic nephropathy.

A systematic review on anti-Alzheimer's disease activity of prescription Kangen-karyu.

Traditional Chinese and Japanese medicines have become prime sources of drug discovery and there is a pressing need to investigate the effectiveness of these traditional medicines for modern drug discovery. Recently, among various traditional formulations, studies on Kangen-karyu (Guan-Yuan-Ke-Li), a mixture of six medicinal herbs (Salviae Miltiorrhizae Radix, Cnidii Rhizoma, Paeoniae Radix, Carthami Flos, Aucklandiae Radix, and Cyperi Rhizoma), have been growing to assess its neuroprotective role. This prompted us to undertake a thorough review of various targets of Kangen-karyu regarding its effectiveness against Alzheimer's disease, particularly focusing on cholinesterases, beta-site amyloid precursor protein cleaving enzyme 1, and glycogen synthase kinase 3ß. This review provides new insights into Kangen-karyu medication as a prospective anti-Alzheimer's medication and indicates the need for in-depth in vivo investigation in the future.

Efficacy of Chinese prescription Kangen-karyu for patient with metabolic syndrome.

Metabolic syndrome is a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus. The risk factors include hypertension, dyslipidemia, hyperglycemia, and central obesity. Various diagnostic criteria have been proposed by different organizations over the past decade. The utilization of traditional Chinese medicine to treat metabolic syndrome has received increasing attention due to its wide availability. In this paper, we report the case of a 68-year-old patient with hypertension, hypercholesterolemia, borderline diabetes, and obesity, who showed an improvement in metabolic syndrome on the administration of 7.5 g of Kangen-karyu extract per day. After 6 months, the levels of serum total cholesterol, low-density lipoprotein-cholesterol, triglycerides, hemoglobin A1c were decreased. The abdominal circumference and body weight were decreased following administration. At that time, the somatic and subjective symptoms had partially disappeared. Herein, we present and discuss the evidence supporting the use of Kangen-karyu extract against metabolic syndrome.

Caterpillar Medicinal Mushroom, Cordyceps militaris (Ascomycetes), Protects Aß1-42-Induced Neurologic Damage in C6 Glial Cells.

Alzheimer's disease (AD) shows neurological symptoms common to cognitive disorders and memory loss. Several hypotheses have suggested that the accumulation of amyloid-beta peptide (Aß) and reduction of acetylcholine synthesis cause AD. Natural ingredients, such as Cordyceps militaris, have been widely used for AD treatment. Herein, we investigated the protective role of C. militaris against neural dysfunction. First, Aß1-42 peptide solution was incubated at 37°C for 3 days for aggregation. Next, C6 glial cells were treated with 25 µM of Aß1-42 solution, followed by the addition of C. militaris ethanol extract (0.5, 1, 1.25, and 2.5 µg/mL); the cell viability, reactive oxygen species (ROS) production, and protein expressions were then evaluated. Reduction of viability of, and ROS generation in, Aß1-42-treated cells were observed and compared with those in the control group. The expression levels of inducible nitric oxide synthase and cyclooxygenase-2, as well as those of phospho-p38 mitogen-activated protein kinase and phospho-c-Jun N-terminal kinase, were reduced in C. militaris-treated glial cells. Moreover, the expression of brain-derived neurotrophic factor in the C. militaris-treated cells was significantly higher than that in the control group. Thus, our findings indicate that C. militaris has the potential to protect Aß-induced neurological damage.

Root Bark of Paeonia suffruticosa Extract and Its Component Methyl Gallate Possess Peroxynitrite Scavenging Activity and Anti-inflammatory Properties through NF-κB Inhibition in LPS-treated Mice.

A peroxynitrite (ONOO-)-generating system induced by 3-morpholinosydnonimine, was used to evaluate the ONOO- scavenging properties of plants that have been widely used as traditional medicine in Korea for the treatment of several diseases. The most effective medicinal plants were Paeonia suffruticosa Andrew, followed in order by Lonicera japonica Thunb., Curcuma zedoaria (Christm.) Roscoe, and Pueraria thunbergiana Benth. In addition, root bark of P. suffruticosa was partitioned with organic solvents of different polarities, and the ethyl acetate (EtOAc) fraction showed the strongest ONOO- scavenging activity. Methyl gallate, a plant-derived phenolic compound identified from the EtOAc fraction, exerted strong ONOO- scavenging activity. The in vivo therapeutic potential of methyl gallate was investigated using lipopolysaccharide-treated mice. Oral administration of methyl gallate protected against acute renal injury and exhibited potential anti-inflammatory properties through an increase in antioxidant activity and decrease in nuclear factor-kappa B activity.

Safflower (Carthamus tinctorius L.) seed attenuates memory impairment induced by scopolamine in mice via regulation of cholinergic dysfunction and oxidative stress.

Cholinergic dysfunction and oxidative stress are the most common causes of Alzheimer's disease (AD). Safflower seed contains various anti-oxidant and cholinergic improvement compounds, such as serotonin and its derivatives. In the present study, we investigated the protective effects and mechanisms of a safflower seed extract on scopolamine-induced memory impairment in a mouse model. The safflower seed extract was orally administered at a dose of 100 mg kg-1 day-1, and then behavior tests (such as T-maze and novel object recognition tests) were conducted. Acetyl cholinesterase (AChE) activity, reactive oxygen species (ROS) production, and antioxidant enzymes in the brain were measured. In behavior tests, the novel route exploration and object recognition were improved by the administration of the safflower seed extract, which suggests that the safflower seed extract improves memory function in the scopolamine-treated mouse model. In addition, the safflower seed extract-administered group showed inhibition of the AChE activity and improved cholinergic dysfunction. Furthermore, the administration of the safflower seed extract resulted in lower ROS production and higher antioxidant enzyme levels as compared to the scopolamine-treated group, suggesting the protective role of the safflower seed extract against oxidative stress. The results of the present study suggest that the safflower seed extract improves scopolamine-induced memory deficits via the inhibition of cholinergic dysfunction and oxidative stress. Therefore, safflower seeds might become a promising agent for memory improvement in AD patients.

Protective Effects of Serotonin and its Derivatives, N-Feruloylserotonin and N-(p-Coumaroyl) Serotonin, Against Cisplatin-Induced Renal Damage in Mice.

This study examined whether serotonin and two of its derivatives, N -feruloylserotonin and N -( p -coumaroyl) serotonin, have a renoprotective effect in a mouse model of cisplatin-induced acute renal failure. Cisplatin (20 mg/kg body weight) was administered by intraperitoneal injection to male BALB/c mice that had received oral serotonin, N -feruloylserotonin or N -( p -coumaroyl) serotonin (7.5 mg/kg body weight per day) during the preceding 2 days. At 3 days after the cisplatin injection, serum and renal biochemical factors, oxidative stress, inflammation and apoptosis-related protein expression were evaluated, and histological examinations were performed. Cisplatin caused reduction in body weight and an increase in kidney weight; however, N -( p -coumaroyl) serotonin and N -feruloylserotonin attenuated these effects. Moreover, the serotonin derivatives significantly decreased serum urea nitrogen and creatinine levels. They also significantly reduced the level of reactive oxygen species and upregulated the expression of glutathione peroxidase in the kidney. Furthermore, the serotonin derivatives improved the abnormal expression of mitogen-activated protein kinases activation-dependent inflammation- and apoptosis-related protein and caused less renal damage. These results provide important evidence that N -( p -coumaroyl) serotonin and N -feruloylserotonin exert a pleiotropic effect on several parameters related to oxidative stress, inflammation and apoptosis. The derivatives also have a renoprotective effect in cisplatin-treated mice; however, this effect is higher with N -( p -coumaroyl) serotonin.

Recirculating peritoneal dialysis system using urease-fixed silk fibroin membrane filter with spherical carbonaceous adsorbent.

The chronic kidney disease (CKD) patients are undergoing continuous ambulatory peritoneal dialysis (CAPD). However, there are some constraints, the frequent exchange of the dialysate and limitation of outside activity, associated with CAPD remain to be solved. In this study, we designed the wearable artificial kidney (WAK) system for peritoneal dialysis (PD) using urease-immobilized silk fibroin (SF) membrane and polymer-based spherical carbonaceous adsorbent (PSCA). We evaluated this kit's removal abilities of uremic toxins such as urea, creatinine, uric acid, phosphorus, and ß2-microglobulin from the dialysate of end-stage renal disease (ESRD) patients in vitro. The uremic toxins including urea, creatinine, uric acid, and phosphorus were removed about 99% by immobilized SF membrane and PSCA filter after 24 h treatment. However, only 50% of ß2-microglobulin was removed by this filtering system after 24 h treatment. In vivo study result shows that our filtering system has more uremic toxins removal efficiency than exchanged dialysate at every 6 h. We suggest that recirculating PD system using urease-immobilized SF membrane with PSCA could be more efficient than traditional dialysate exchange system for a WAK for PD.

Safflower seed extract synergizes the therapeutic effect of cisplatin and reduces cisplatin-induced nephrotoxicity in human colorectal carcinoma RKO cells and RKO-transplanted mice.

Safflower seed is effective against oxidative stress, mediating the activation of the apoptotic signaling pathway in the renal tissues of cisplatin-treated mice. The anticancer activity of safflower in various cancer cell lines has also been reported. The present study was conducted to evaluate the potential synergistic anticancer effects of the co-treatment of safflower seed extracts and cisplatin in RKO cells and in BALB/c mice bearing RKO cell-derived human colorectal tumors. In the cellular system, RKO cells were treated with safflower seed extract in the presence or absence of cisplatin for 48 h and the cytotoxicity was evaluated by using microscopy. In the in vivo system, mice were injected with RKO cells and subsequently orally administered 100 or 200 mg/kg body weight safflower seed extract plus cisplatin-treated or untreated mice for 3 days to examine the inhibitory effect on the tumor. Treatment with safflower seed extract or cisplain to RKO cells resulted in a greater cell death than in with untreated cells. In the RKO cells co-treated with both safflower seed extract and cisplatin, greater cell damage was observed. In addition, mice co-administered safflower seed extract and cisplatin had lower concentrations of serum creatinine, which were indicative of less damage to the kidney, and had a lower solid tumor mass and higher expression of the caspase-3 protein. The results showed that safflower seed extract was highly toxic to RKO cells and inhibited tumor growth in cisplatin-treated mice through renoprotective effects.

Rosmarinic Acid Derivatives' Inhibition of Glycogen Synthase Kinase-3ß Is the Pharmacological Basis of Kangen-Karyu in Alzheimer's Disease.

Inhibition of glycogen synthase kinase 3ß (GSK-3ß) is considered to be the central therapeutic approach against Alzheimer's disease (AD). In the present study, boiled water extracts of the Kangen-karyu (KK) herbal mixture and its constituents were screened for GSK-3ß inhibitory activity. KK is used in traditional Kampo and Chinese medicines for improving cognitive function. The GSK-3ß inhibition potential was evaluated by using the Kinase-Glo luminescent kinase assay platform. Furthermore, enzyme kinetics and in silico modeling were performed by using AutoDockTools to demonstrate the mechanism of enzyme inhibition. KK extract significantly inhibited GSK-3ß in a concentration-dependent manner (IC50: 17.05 ± 1.14 µg/mL) when compared with the reference drug luteolin (IC50: 2.18 ± 0.13 µM). Among the six components of KK, extracts of Cyperi Rhizoma and Salviae Miltiorrhizae Radix significantly inhibited GSK-3ß with IC50 values of 20.68 ± 2.50 and 7.77 ± 1.38 µg/mL, respectively. Among the constituents of the roots of S. miltiorrhiza water extract, rosmarinic acid, magnesium lithospermate B, salvianolic acid A, salvianolic acid B, and salvianolic acid C inhibited GSK-3ß with IC50 values ranging from 6.97 to 135.5 µM. Salvianolic acid B was found to be an ATP-competitive inhibitor of GSK-3ß and showed the lowest IC50 value (6.97 ± 0.96 µM). In silico modeling suggested a mechanism of action by which the hydrophobic, π⁻cation, and hydrophilic interactions of salvianolic acid B at ATP and substrate sites are critical for the observed GSK-3ß inhibition. Therefore, one of the mechanisms of action of KK against AD may be the inhibition of GSK-3ß and one of the active components of KK is the root of S. miltiorrhiza and its constituents: rosmarinic acid, magnesium lithospermate B, and salvianolic acids A, B, and C. Our results demonstrate the pharmacological basis for the use of KK against AD.

Oligonol, a low-molecular-weight polyphenol derived from lychee peel, attenuates diabetes-induced pancreatic damage by inhibiting inflammatory responses via oxidative stress-dependent mitogen-activated protein kinase/nuclear factor-kappa B signaling.

This study investigated the effects of oligonol, a low-molecular-polyphenol derived from lychee peel, against diabetes-induced pancreatic damage via oxidative stress-induced inflammation. Oligonol was orally administered at 10 or 20 mg/kg body weight/day for 10 days to streptozotocin-induced diabetic rats, and the rats were compared with nondiabetic and diabetic control rats. The diabetic rats showed loss of body weight and increased pancreatic weight, and the oral administration of oligonol attenuated these parameters. Moreover, the administration of oligonol caused a significant decrease in the serum glucose level and a significant increase in the serum and pancreatic insulin and C-peptide levels in the diabetic rats. Oligonol also significantly reduced the enhanced levels of reactive oxygen species and 2-thiobarbituric acid reactive substance, which are oxidative stress biomarkers, in the serum and pancreas. Oligonol treatment reduced the overexpression of phospho-p38, phospho-ERK1/2, phospho-inhibitor of nuclear factor-kappa B (NF-κB), NF-κBp65, and NF-κBp65-induced inflammatory protein such as cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6. Furthermore, oligonol treatment led to significantly attenuated histological damage in the pancreas. On the basis of these results, we conclude that a plausible mechanism of oligonol's antidiabetic action may be its antioxidative stress-related anti-inflammatory action.

Increase in the hydroxyl radical-scavenging activity of Panax ginseng and ginsenosides by heat-processing.

Panax ginseng C.A. Meyer (Araliaceae), mainly cultivated in Korea and Northeast China, is processed before use based on its long history of ethnopharmacological evidence. Ginsenosides have been regarded as the main active components responsible for the pharmacological activities of ginseng. Although the Maillard reaction is known as a major source of compounds related to enhanced antioxidant activity by heat treatment in various crude drugs or foods, the chemical and free radical-scavenging activity changes of ginsenosides brought about by the Maillard reaction have not yet been elucidated. This paper gives a review of our recent findings, with emphasis on the hydroxyl radical (•OH)-scavenging activity changes of ginsengs and ginsenosides by heat-processing using an electron spin resonance spectrometer. 20(S)- Rg3 showed the strongest activity, and the next was in the decreasing order of Rb1, Rg1, Rc, Rb2, and Rd. The •OH-scavenging activities of ginsenosides were related to the ferrous metal ion-chelating activities of their aglycone, 20(S)-protopanaxadiol. In addition, the ferrous metal ion-chelating activities of ginsenosides were thought to be influenced by their types of hydrophilic sugar moieties. Moreover, Rb1 was changed into 20(S)-Rg3, 20(R)-Rg3, Rk1, and Rg5 by heat-processing, and the sugar moieties at carbon-20 were separated. The generated amount of 20(S)-Rg3 was higher than when Rb1 was heat-processed without amino acids, and a significant increase in Maillard reaction products was noted. Based upon chemical and •OH-scavenging activity tests using Maillard reaction model experiments, the scientific evidence underlying the increase in free radical-scavenging activity of ginseng induced by heat-processing was elucidated.

Comparison of the Effects of Nonfermented and Fermented Panax ginseng Root Against Hypertriglycemia in High-Fat Diet-Fed Mice.

Panax ginseng (P. ginseng C.A. Meyer, Araliaceae) is used as a therapeutic agent for various diseases. P. ginseng saponins, known as ginsenosides, are the main bioactive compounds responsible for its pharmacological activities. In this work, we have developed a new method of P. ginseng root processing termed solid-state fermentation and examined its effects compared with nonfermented P. ginseng. Mice were fed a high-fat diet (HFD) to induce hyperlipidemia and then received 100 mg·kg bw-1·day-1 of fermented or nonfermented P. ginseng orally for 3 weeks. We assessed the activities of lipogenic pathways and lipid levels in the liver and plasma. The administration of either nonfermented or fermented P. ginseng improved hepatic lipid transfer protein profiles. Nonfermented P. ginseng exhibited significant effects on the regulation of lipid synthesis and oxidation. However, apolipoprotein A4 (apoA4) expression was increased by the administration of fermented P. ginseng. When ginsenosides were analyzed by high-performance liquid chromatography (HPLC), the amounts of the ginsenosides, Rg2, Rc, Rh1(S), Rh1(R), and Rd, were increased by fermentation, with Rd becoming a major constituent of fermented P. ginseng. These findings imply that nonfermented P. ginseng improves hypertriglycemia in HFD-fed mice through regulation of the hepatic lipogenic pathway. In contrast, the effects of fermented P. ginseng were mediated through increased apoA4, leading to decreased triglycerides. The HPLC profiles of ginsenosides suggest that the compositional changes in P. ginseng caused by fermentation processing could be useful in the development of novel triglyceride-lowering therapies.

Protective Effect of Safflower Seed on Cisplatin-Induced Renal Damage in Mice via Oxidative Stress and Apoptosis-Mediated Pathways.

Cisplatin, a platinum chelate with potent antitumor activity against cancers of the testis, ovary, urinary bladder, prostate, and head and neck, has adverse effects on the kidney, bone marrow, and digestive organs, and its use is particularly limited by nephropathy as a side effect. In the present study, safflower seed extract was administered to a mouse model of cisplatin-induced acute renal failure to investigate its activity. Cisplatin (20[Formula: see text]mg/kg body weight) was administered by intraperitoneal injection to mice that had received oral safflower seed extract (100 or 200[Formula: see text]mg/kg body weight per day) for the preceding 2 days. Three days after the cisplatin injection, serum and renal biochemical factors; oxidative stress, inflammation, and apoptosis-related protein expression; and histological findings were evaluated. Cisplatin-treated control mice showed body-weight, food intake and water intake loss, and increased kidney weight, whereas the administration of safflower seed extract attenuated these effects ([Formula: see text], [Formula: see text]). Moreover, safflower seed extract significantly decreased the renal functional parameters urea nitrogen and creatinine in the serum ([Formula: see text] and [Formula: see text], respectively). Safflower seed extract also significantly reduced the enhanced levels of reactive oxygen species in the kidney observed following cisplatin treatment, with significance. The expression of proteins related to the anti-oxidant defense system in the kidney was down-regulated following cisplatin treatment, but safflower seed extract significantly up-regulated the expression of the anti-oxidant enzyme catalase. Furthermore, safflower seed extract reduced the overexpression of phosphor (p)-p38, nuclear factor-kappa B p65, cyclooxygenase-2, inducible nitric oxide synthase, ATR, p-p53, Bax, and caspase 3 proteins, and mice treated with safflower seed extract exhibited less renal histological damage. These results provide important evidence that safflower seed extract exerts a pleiotropic effect on several oxidative stress- and apoptosis-related parameters and has a renoprotective effect in cisplatin-treated mice.

Heat-Processed Scutellariae Radix Protects Hepatic Inflammation through the Amelioration of Oxidative Stress in Lipopolysaccharide-Induced Mice.

The present study evaluated the effects of heat-processed Scutellariae Radix (Scutellaria baicalensis) on lipopolysaccharide (LPS)-induced liver injury in mice. Scutellariae Radix heat-processed at 160[Formula: see text]C or 180[Formula: see text]C was orally administered at a dose of 100 mg/kg body weight for three days before the intraperitoneal injection of LPS, and the effects were compared with those of vehicle-treated LPS administered to control mice. The administration of Scutellariae Radix decreased the elevated serum monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), reactive oxygen species (ROS), nitrite/nitrate, peroxynitrite, and hepatic functional parameters, and reduced the increased ROS in the liver. The augmented expressions of hepatic oxidative stress and inflammation-related proteins, phospho-p38, phosphorylated extracellular signal-regulated kinase, phosphorylated c-Jun N-terminal kinase, nuclear factor-[Formula: see text] B p65, activator protein-1, cyclooxygenase-2, inducible nitric oxide synthase, MCP-1, intercellular adhesion molecule-1, tumor necrosis factor-[Formula: see text], and IL-6, were downregulated by the heat-processed Scutellariae Radix. Hematoxylin-eosin staining showed that the increased hepatocellular damage in the liver of LPS-treated mice improved with the administration of heat-processed Scutellariae Radix. Overall, the ameliorative effects of Scutellariae Radix were superior to those when heat-processed at 180[Formula: see text]C. Our results indicate that heat-processed Scutellariae Radix acts as an anti-inflammatory agent by ameliorating oxidative stress in the liver of mice with LPS-induced liver injury.