Project description:Houttuyniae herba, the Saururaceae plant Houttuynia cordata Thunb., has multiple therapeutic effects, including clearing heat, eliminating toxins, reducing swelling, discharging pus, and relieving stagnation. It has a long history as an edible and medicinal plant in China. Phytochemical studies show that the main constituents include volatile oil, flavonoids, and alkaloids. Aristolactam is a major alkaloid with a structure similar to toxic aristolochic acids. However, there has been no systematic study on aristolochic acids and alkaloids in Houttuyniae herba. Therefore, in this study, an LC-MS/MS method was developed to simultaneously detect seven alkaloids and five aristolochic acids in Houttuyniae herba from different origins. Six alkaloids (O-demethyl nornucifrine, N-nornucifrine, aristololactam AII, aristololactam FI, aristololactam BII, cepharadione B) were found and quantitatively determined in 75 batches of samples. Meanwhile, no aristolochic acids or aristololactams were found in Houttuyniae herba at a limit of detection (LOD) of ≤4 ng/mL. The method developed was fully validated in terms of LOD, limit of quantification (LOQ), linearity, precision, accuracy, and stability. These data clarify the content of the above safety-related components in Houttuyniae herba and provide a reference for further research into its safety.
Project description:Hyperlipidemia is associated with metabolic disorders, but the detailed mechanisms and related interventions remain largely unclear. As a functional food in Asian diets, Herba houttuyniae has been reported to have beneficial effects on health. The present research was to investigate the protective effects of Herba houttuyniae aqueous extract (HAE) on hyperlipidemia-induced liver and heart impairments and its potential mechanisms. Male C57BL/6J mice were administered with 200 or 400 mg/kg/day HAE for 9 days, followed by intraperitoneal injection with 0.5 g/kg poloxamer 407 to induce acute hyperlipidemia. HAE treatment significantly attenuated excessive serum lipids and tissue damage markers, prevented hepatic lipid deposition, improved cardiac remodeling, and ameliorated hepatic and cardiac oxidative stress induced by hyperlipidemia. More importantly, NF-E2 related factor (Nrf2)-mediated antioxidant and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α)-mediated mitochondrial biogenesis pathways as well as mitochondrial complex activities were downregulated in the hyperlipidemic mouse livers and hearts, which may be attributable to the loss of adenosine monophosphate (AMP)-activated protein kinase (AMPK) activity: all of these changes were reversed by HAE supplementation. Our findings link the AMPK/PGC-1α/Nrf2 cascade to hyperlipidemia-induced liver and heart impairments and demonstrate the protective effect of HAE as an AMPK activator in the prevention of hyperlipidemia-related diseases.
Project description:Houttuyniae herba has a long history of medicinal and edible homology in China. It has the functions of clearing heat and detoxifying, reducing swelling and purulent discharge, diuresis, and relieving gonorrhea. It is mainly distributed in the central, southeastern, and southwestern provinces of China. Houttuyniae herba has been designated by the National Ministry of Health of China as a dual-use plant for both food and medicine. Comprising volatile oils, flavonoids, and alkaloids as its primary constituents, Houttuyniae herba harbors aristolactams, a prominent subclass of alkaloids. Notably, the structural affinity of aristolactams to aristolochic acids is discernible, the latter known for its explicit toxicological effects. Additionally, the safety study on Houttuyniae herba mainly focused on the ethanol, methanol, or aqueous extract. In this study, both zebrafish and mice were used to evaluate the acute toxicity of the total alkaloids extracts from Houttuyniae herba (HHTAE). The zebrafish experiment showed that a high concentration (0.1 mg/mL) of HHTAE had a lethal effect on zebrafish embryos. Furthermore, the mice experiment results showed that, even at a higher dose of 2000 mg/kg, HHTAE was not toxic. In conclusion, HHTAE was of low safety risk.
Project description:ObjectiveInflammation and fibrosis are essential promoters in the pathogenesis of diabetic nephropathy (DN) in type 2 diabetes. The present study examined the anti-inflammation and anti-fibrosis effect of Tangshen Formula (TSF), a traditional Chinese medicine, on DN.Research design and methodsProtective role of TSF in DN was examined in a rat model of type 2 DN that was established by high-fat diet-fed and low-dose-streptozotocin injection. TSF was suspended in 0.5% CMC-Na solution and delivered by oral gavage at a dosage of 1.67g/Kg body weight/day. The therapeutic effects and mechanisms of TSF on diabetic kidney injury were examined.ResultsWe found that TSF treatment for 20 weeks attenuated DN by significantly inhibiting urinary excretion of albumin and renal histological injuries. These beneficial effects were associated with an inactivation of NF-κB signaling, thereby blocking the upregulation of pro-inflammatory cytokines (IL-1β, TNFα), chemokine (MCP-1), and macrophage infiltration in the TSF-treated rats with type 2 DN. In addition, TSF treatment also inactivated TGF-β/Smad3 signaling and therefore suppressed renal fibrosis including expressions of fibronectin, collagen I, and collagen IV. Further studies revealed that the inhibitory effect of TSF on TGF-β/Smad3 and NF-κB signaling in DN was associated with inhibition of Smurf2-dependent ubiquitin degradation of Smad7.ConclusionsThe present study reveals that TSF has therapeutic potential for type 2 DN in rats. Blockade of NF-κB-driven renal inflammation and TGF-β/Smad3-mediated renal fibrosis by preventing the Smurf2-mediated Smad7 degradation pathway may be mechanisms through which TSF inhibits type 2 DN.
Project description:Background and aimIn the present study, we investigate the phytochemical composition and the nephroprotective effects as well as the antioxidant properties of Artemisia herba alba aqueous extract in alloxan-induced experimental diabetes in rats.Experimental procedureWistar rats were divided into four groups of seven rats each: Group I: Normal control (NC) received saline solution at 9‰ given by intraperitoneal way; Group II: Diabetic control (DC) received alloxan (150 mg/kg b.w) intraperitoneally; Group III: Normal control (NC + AHA) received saline solution at 9‰ and treated orally by AHA aqueous extract (400 mg/kg/b.w); Group IV: Diabetic control (DC + AHA) received alloxan solution (150 mg/kg b.w) intraperitoneally and treated by aqueous extract of AHA (400 mg/kg/b.w/day) orally after one week of alloxan administration. After 30 days, blood and tissue samples were collected for biochemical and histopathological analysis, respectively. Glomerular damage markers, including creatinine, serum urea, urine creatinine and urine urea levels were estimated. Creatinine clearance was also assessed. Oxidative stress parameters were assessed in the kidney homogenate.Results and conclusionAlloxan-exposure resulted in significant increase in blood glucose and serum level of glomerular damage markers. The antioxidant enzyme activities were significantly downregulated associated with an increase in malondialdehyde (MDA) level over the baseline values. Artemisia herba alba aqueous extract supplementation significantly improved the studied parameters. In concluding, the results obtained suggests that Artemisia herbs-alba aqueous extract supplementation reduces alloxan-induced free radical generation, potentiates the antioxidant defense system and alleviates renal sensitivity to oxidative stress.
Project description:Dietary intervention is crucial for the prevention and control of diabetes. China has the largest diabetic population in the world, yet no one dietary strategy matches the eating habits of the Chinese people. To explore an effective and acceptable dietary pattern, this study uses oat and buckwheat compound (OBC) as a staple food substitute and explored its effects on diabetic Sprague-Dawley rats. The model of diabetic rats was established by combining high-calorie feed and streptozotocin (STZ) injection. The dietary intervention for the seven groups, including a normal control group, a model control group, a metformin control group, a wheat flour control group, and three OBC groups with different doses, started from the beginning of the experiment and lasted for 11 weeks, two consecutive injections of STZ in small doses were operated at the 6th week. General states, glucose metabolism, and lipid metabolism indexes were measured. Antioxidant and inflammatory indexes and pathologic changes of kidney and liver tissues were tested. Changes in kidney and ileum ultramicrostructure were detected. What's more, ileal epithelial tight junction proteins and gut microbiota were analyzed. Significant decreases in fasting blood glucose (FBG), glucose tolerance, serum insulin, and insulin resistance were observed in rats intervened with OBC, and these rats also showed a higher level of superoxide dismutase (SOD) together with improved lipid metabolism, attenuated inflammation, and liver and kidney injuries. In addition, in OBC groups, the intestinal barrier was improved, and the disturbance of gut microbiota was reduced. These results suggest that OBC has health-promoting effects for diabetic rats, and since oat and buckwheat are traditionally consumed grains in China, OBC could be a potential and easy-to-accept staple food substitute for the dietary pattern for Chinese.
Project description:Superoxide anion (O(2) (•-)) is overproduced in joint inflammation, rheumatoid arthritis, and osteoarthritis. Increased O(2) (•-) production leads to tissue damage, articular degeneration, and pain. In these conditions, the physiological defense against O(2) (•-), superoxide dismutases (SOD) are decreased. The Mn(II) complex MnL4 is a potent SOD mimetic, and in this study it was tested in inflammatory and osteoarticular rat pain models. In vivo protocols were approved by the animal Ethical Committee of the University of Florence. Pain was measured by paw pressure and hind limb weight bearing alterations tests. MnL4 (15 mg kg(-1)) acutely administered, significantly reduced pain induced by carrageenan, complete Freund's adjuvant (CFA), and sodium monoiodoacetate (MIA). In CFA and MIA protocols, it ameliorated the alteration of postural equilibrium. When administered by osmotic pump in the MIA osteoarthritis, MnL4 reduced pain, articular derangement, plasma TNF alpha levels, and protein carbonylation. The scaffold ring was ineffective. MnL4 (10(-7) M) prevented the lipid peroxidation of isolated human chondrocytes when O(2) (•-) was produced by RAW 264.7. MnL4 behaves as a potent pain reliever in acute inflammatory and chronic articular pain, being its efficacy related to antioxidant property. Therefore MnL4 appears as a novel protective compound potentially suitable for the treatment of joint diseases.
Project description:Hydrogen sulfide (H₂S) is involved in the pathophysiology of type 2 diabetes. Inhibition and stimulation of H₂S synthesis has been suggested to be a potential therapeutic approach for type 2 diabetes. The aim of this study was therefore to determine the effects of long-term sodium hydrosulfide (NaSH) administration as a H₂S releasing agent on carbohydrate metabolism in type 2 diabetic rats. Type 2 diabetes was established using high fat-low dose streptozotocin. Rats were treated for 9 weeks with intraperitoneal injections of NaSH (0.28, 0.56, 1.6, 2.8, and 5.6 mg/kg). Serum glucose was measured weekly for one month and then at the end of the study. Serum insulin was measured before and after the treatment. At the end of the study, glucose tolerance, pyruvate tolerance and insulin secretion were determined and blood pressure was measured. In diabetic rats NaSH at 1.6⁻5.6 mg/kg increased serum glucose (11%, 28%, and 51%, respectively) and decreased serum insulin, glucose tolerance, pyruvate tolerance and in vivo insulin secretion. In controls, NaSH only at 5.6 mg/kg increased serum glucose and decreased glucose tolerance, pyruvate tolerance and insulin secretion. Chronic administration of NaSH in particular at high doses impaired carbohydrate metabolism in type 2 diabetic rats.
Project description:Scope: Diabetic retinopathy (DR) is a severe microvascular complication of diabetes. Previous clinical trials have shown that Compound Danshen Dripping Pill (CDDP) improves DR symptoms. However, the mechanism involved remains unclear. Procedures: Rats fed a high-fat diet and injected with streptozotocin (STZ) were used as an experimental type 2 diabetes rodent model. CDDP was administered to two groups of diabetic rats at 0.2 and 0.4 g/kg/day via gastric gavage for 12 weeks. After the 12 weeks of treatment, retinal function was evaluated by electroretinography (ERG). Histological staining and TdT-mediated dUTP nick-end labeling (TUNEL) assays were also performed. Retinal genome expression was determined by gene array. Results: We found that CDDP moderated ERG and histological abnormalities in diabetic rats, independent of blood glucose level. A gene array showed that CDDP changed 262 genes significantly in the diabetic retina. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that differentially expressed genes in the CDDP-treated groups were involved mainly in the apoptosis pathway. Moreover, CDDP reduced the number of TUNEL-positive cells in the diabetic retinas. CDDP prevented the reduction in Bcl-2 expression and the increase in BCL-2 associated X (Bax) and caspase-3 (Casp3) expression in diabetic rats. Conclusion: Our results suggest that CDDP exerts its neuroprotective functions by inhibiting cell apoptosis in diabetic rats.
Project description:Introduction: In the current study, the effects of photobiomodulation (PBM) treatments were examined based on biomechanical and histological criteria and mRNA levels of catalase (CAT), superoxide dismutase (SOD), and NADPH oxidase (NOX) 1 and 4 in a postponed, ischemic, and infected wound repair model (DIIWHM) in rats with type 2 diabetes (DM2) during the inflammation (day 4) and proliferation (day 8) stages. Methods: To study ischemic wound repair in a diabetic rat model (DIIWHM), 24 rats with type-2 diabetes were randomly divided into four groups and infected with methicillin-resistant Staphylococcus aureus (MRSA). The control groups consisted of CG4 (control group on day 4) and CG8 (control group on day 8), while the PBM groups comprised PBM4 (PBM treatment group on day 4) and PBM8 (PBM treatment group on day 8). These group assignments allowed for comparisons between the control groups and the PBM-treated groups at their respective time points during the study. Results: On days 4 and 8 of wound restoration, the PBM4 and PBM8 groups showed substantially modulated inflammatory responses and improved formation of fibroblast tissue compared with the CG groups (P<0.05). Concurrently, the effects of PBM8 were significantly superior to those of PBM4 (P<0.05). The antioxidant results on days 4 and 8 revealed substantial increases in CAT and SOD in the PBM groups compared with the CGs (P<0.05). Substantial decreases were observed in the antioxidant agents NOX1 and NOX4 of the PBM4 and PBM8 groups compared with both CGgroups (P<0.05). Conclusion: PBM treatments significantly sped up the inflammatory and proliferating processes in a DHIIWM in DM2 animals by modifying the inflammatory reaction and boosting fibroblast proliferation. Overall, the current findings indicated substantially better results in the PBM groups than in the CG groups.