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The biological function of the natural ent-kaurene diterpenoid isolated from genus Isodon, oridonin, has been intensively studied. However, its mechanism studies and clinical applications were hampered by its moderate biological activities. In order to enlarge the applied range of oridonin and explore its mechanism of action, a series of derivatives were designed and synthesized based on the structure of oridonin. Some of the derivatives were significantly more potent than oridonin against four cancer cell lines. Especially, the most potent compound 20 markedly inhibited the proliferation of well differentiated HepG2 and poorly differentiated PLC/PRF/5 cells, with IC50 values as low as 1.36 μM and 0.78 μM respectively, while the IC50 values of oridonin are 8.12 μM and 7.41 μM. We found that compound 20 inhibited liver cancer cell proliferation via arresting cell cycle at G1 phase. Moreover, it induced liver cancer cell apoptosis by decreasing the mitochondrial membrane potential, increasing intracellular reactive oxygen species level and inducing the expression of apoptosis-related proteins. Furthermore, compound 20 significantly inhibited growth of PLC/PRF/5 xenograft tumors in nude mice and had no observable toxic effect. Altogether, these results indicated that compound 20 is a promising lead for liver cancer therapeutics.

Maltol, a maillard reaction product from ginseng (Panax ginseng C. A. Meyer), has been confirmed to inhibit oxidative stress in several animal models. Its beneficial effect on oxidative stress related brain aging is still unclear. In this study, the mouse model of d-galactose (d-Gal)-induced brain aging was employed to investigate the therapeutic effects and potential mechanisms of maltol. Maltol treatment significantly restored memory impairment in mice as determined by the Morris water maze tests. Long-term d-Gal treatment reduced expression of cholinergic regulators, i.e., the cholineacetyltransferase (ChAT) (0.456 ± 0.10 vs 0.211 ± 0.03 U/mg prot), the acetylcholinesterase (AChE) (36.4 ± 5.21 vs 66.5 ± 9.96 U/g). Maltol treatment prevented the reduction of ChAT and AChE in the hippocampus. Maltol decreased oxidative stress levels by reducing levels of reactive oxygen species (ROS) and malondialdehyde (MDA) production in the brain and by elevating antioxidative enzymes. Furthermore, maltol treatment minimized oxidative stress by increasing the phosphorylation levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), nuclear factor-erythroid 2-related factor 2 (Nrf2), and hemeoxygenase-1 (HO-1). The above results clearly indicate that supplementation of maltol diminishes d-Gal-induced behavioral dysfunction and neurological deficits via activation of the PI3K/Akt-mediated Nrf2/HO-1 signaling pathway in brain. Maltol might become a potential drug to slow the brain aging process and stimulate endogenous antioxidant defense capacity. This study provides the novel evidence that maltol may slow age-associated brain aging.

Successive evidence has established that maltol, a flavor-enhancing agent, could provide resistance to oxidative stress-induced tissue injury in various animal models though its benefits for aging-induced liver and kidney injuries are still undetermined. In the present work, for demonstrating maltol's ameliorative effect and probable mechanism against aging-induced liver and kidney injuries, D-galactose (D-Gal)-induced animal in vivo and HEK293 cells in vitro models were established and results demonstrated that long-term D-Gal treatment increases the accumulation of advanced glycation end products (AGEs) in liver and kidney tissues, mitigates cell viability, and arrests the cycle. Interestingly, 4-weeks maltol treatment at 50 and 100 mg/kg activated aging-associated proteins including p53, p21, and p16 followed by inhibiting malondialdehyde (MDA)'s over-production and increasing the levels of antioxidant enzymes. Therefore, decreases in cytochrome P450 E1 (CYP2E1) and 4-hydroxydecene (4-HNE)'s immunofluorescence expression levels are confirmed. Furthermore, maltol improved oxidative stress injury by activating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. In conclusion, the purpose of the present study was to estimate the mechanistic insights into maltol's role as an antioxidant in liver and kidney cell senescence and injury, which will reflect potential of therapeutic strategy for antiaging and aging-related disease treatment.

Although growing evidence has shown that ginseng (Panax ginseng C.A. Meyer.) exerts strong protective and preventive effects on cisplatin-induced side effects, including nephrotoxicity, ototoxicity and cardiotoxicity, the ameliorative effects of ginseng on intestinal damage caused by cisplatin are unknown to date. Red ginseng (RG), a major processed product of the roots of Panax ginseng C.A. Meyer, can be used to control chemotherapy drug-induced multiple toxicity. In the present work, an animal model of cisplatin-induced intestinal injury was established to evaluate the ameliorative effects of RG and their underlying molecular mechanism for the first time. The results showed that a single cisplatin injection (20 mg kg−1) leads to loss of body weight, shrinkage of the small intestine, and sharp increase of the intestinal function index of diamine oxidase (DAO). These symptoms were remarkably relieved after the administration of RG at 300 and 600 mg kg−1 for 10 continuous days, respectively. In addition, RG markedly reduced the increase in malondialdehyde (MDA) levels and the consumption of superoxide dismutase (SOD) and catalase (CAT) caused by cisplatin-induced oxidative stress. Furthermore, RG pretreatment dramatically improved the cisplatin-induced apoptosis of intestinal villous cells, irregular nuclear arrangement, ablation of crypt cells, and damage to the mechanical barrier. In this study, pharmacological methods have been used to prove that RG can inhibit cisplatin intestinal toxicity by activating the PI3K/AKT signaling pathway to inhibit apoptosis and by antagonizing the MAPK-mediated autophagy pathway.

Background Cisplatin is one of the most common chemotherapeutic drugs. Cisplatin-induced toxicity gives rise to gastrointestinal cell damage, subsequent diarrhea and vomiting, leading to the discontinuation of its clinical application in long-term cancer chemotherapy. Panax quinquefolium L., also known as American ginseng, has many pharmacological activities such as improving immunity, anti-tumor, anti-radiation and blood sugar lowering. Purpose Previously, our laboratory reported that American ginseng berry extract could alleviate chemotherapeutic agents-induced renal damage caused by cisplatin. Hence, this study further explored the protective effect of P. quinquefolium saponins (PQS) on cisplatin-induced intestinal injury in mice and the possible molecular mechanisms. Methods Biochemical markers, levels of inflammatory factors, histopathological staining and western blotting were used to analyze intestinal injury based on various molecular mechanisms. Results We demonstrated the destruction of the intestinal barrier caused by cisplatin exposure by detecting the activity of diamine oxidase (DAO) and the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin. Meanwhile, cisplatin exposure changed SOD and MDA levels in the small intestine, causing oxidative damage to the intestinal mucosa. The inflammation associated-intestinal damage was further explored by the measurement of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and analysis of nuclear factor-kappa B (NF-κB) inflammatory pathway protein expression. Moreover, apoptotic cells labeled with TUNEL staining-positive cells and activated caspase family proteins suggest that cisplatin induces intestinal apoptosis. Interestingly, PQS pretreatment significantly reversed these situations. Conclusion These evidence s clearly suggest that PQS can alleviate cisplatin-induced intestinal damage by inhibiting oxidative stress, reducing the occurrence of inflammation and apoptosis, and improving intestinal barrier function.

Acid volatile sulfide (AVS) has been regarded as an important factor controlling metal bioavailability in anoxic sediments, but its effect on metal accumulation under natural conditions is poorly understood. Here, a field study of the influence of AVS on metal accumulation by Limnodrilus sp. in a heavily polluted river is provided. Most of the study area was subject to anaerobic and strongly reducing conditions, and the concentration of trace metals in surface sediments was high, as were the concentration of AVS and simultaneously extracted metals (SEM; average AVS = 20.3 μmol g(-1), average ∑SEM5 = 9.42 μmol g(-1); ∑SEM5 refers to the sum of SEMCd, SEMCu, SEMPb, SEMNi, and SEMZn). Only a few species and small quantities of benthic invertebrates were found, and Limnodrilus sp. was dominant. There was no correlation between trace metal accumulation and (SEM-AVS), and in stations where (SEM-AVS)0, the absolute value of bioaccumulation was high (average ∑BIO5 = 4.07 μmol g(-1); ∑BIO5 refers to the sum of BIOCd, BIOCu, BIOPb, BIONi, and BIOZn), indicating that there was no relationship between (SEM-AVS) and metal accumulation in Limnodrilus sp. This was likely because Limnodrilus sp. ingest sediment particles as their main food source, so pore water metals play a minor role in their bioaccumulation (BIO) of materials. However, ∑BIO5 was significantly correlated with ∑SEM5 (r = 0.795, p 0.01), revealing that the large number of sulfide-bound metals (SEM) in sediments may play an important role in metal accumulation in Limnodrilus sp., which can assimilate sulfide-associated metals by the help of the digestive fluids in the digestive systems.

To study hypoglycemic effects of total flavonoid from Toona sinensis (TSTF) on diabetic mice model.To confect alloxan 0.02 g/ml with NS and injected alloxan into abdominal cavity to induce diabetic model, and all rats were fed bid with glucose for 2 consecutive days, then the blood glucose was detected by glucose oxidizes, when hypoglycemic point11.00 mmol/L the rats were successful model made. 100 model rats were divided into 5 groups as contrast groups (distilled water), model control control groups, hight doses group (0.12 g/kg) and low doses group (0.6 g/kg) of TSTF, positive control groups of phenformin (0.10 g/kg); In addition to set 20 natural rats (distilled water), and all groups were fed qd for 15 consecutive days, and then the blood glucose were detected by glucose oxidizes in the sixteenth day.The blood glucose levels of the diabetic rats in TSTF groups significantly decreased.TSTF can significantly decrease the blood glucose levels of diabetic mice induced by alloxan.