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Red yeast rice (RYR) is known for its lipid-lowering effects in patients with hypercholesterolemia; however, its comparative efficacy with statins and risk reduction remains uncertain. This retrospective study analyzed data from 337,104 patients with hyperlipidemia in the Chang Gung Research Database cohort, spanning from January 2016 to December 2021. Exclusion criteria were applied to ensure data completeness and compliance, including an age limit of < 1 8 years, absence of RYR or statin treatment, and a treatment duration of < 3 0 days. Propensity score matching was employed to minimize bias based on baseline factors, with one patient matching with four patients in the comparison group. The study encompassed a total of 5,984 adult hyperlipidemic patients, with 1,197 in the RYR group and 4,787 in the statin group. The patients were also stratified into statin (n = 8 8 0) or combined use (n = 2 2 0) groups for further comparison. Following one year of treatment, both the RYR and statin groups exhibited reductions in total cholesterol and triglyceride levels. Most biochemical parameters showed no significant differences, except for elevated glutamic oxaloacetic transaminase levels in the RYR group (p = 0. 0 2 6) and increased glycohemoglobin levels in the statin group at the three-month mark (p = 0. 0 3 5). In patients with comorbid diabetes, hypertension, kidney, or liver diseases, RYR and statins demonstrated comparable risks for emergency room (ER) visits, stroke, and myocardial infarction (MI). However, the combination of RYR and statins was associated with reduced stroke-related hospitalizations in patients with diabetes, hypertension, and kidney disease, as well as decreased MI-related hospitalizations in patients with hypertension and kidney disease (all p < 0. 0 0 0 1). In conclusion, both RYR and statins effectively lower blood lipid levels and mitigate related complications. Combining these therapies may lead to fewer ER visits, reduced stroke frequency, and fewer MI hospitalizations in hypertensive and kidney disease patients, and they decreased all-cause mortality in the kidney disease population. Further research on combined therapy is warranted. [ABSTRACT FROM AUTHOR]

Helianthus Annuus L. (HAL) is composed of flavonoids and polysaccharides. Flavonoids have demonstrated beneficial effects on atherosclerosis (AS). The objective of this study was to investigate the anti-atherosclerosis effect and the related mechanism of HAL. In this study, the AS model induced by high-fat diet (HFD) mice that lacked apolipoprotein E (Apoe − / −) received feed containing 5% HAL for 24 weeks. After administration, the analysis of plaque on aorta was conducted, and the possible mechanisms were further explored. With HAL treatment, the size of atherosclerotic lesions in HFD-induced AS model mice was reduced. HAL ameliorated dyslipidemia and decreased the combined ratio. HAL up-regulated concentrations of superoxide dismutase (SOD), nitric oxide (NO) and glutathione peroxidase (GSH-Px) and down-regulated concentrations of malondialdehyde (MDA) in the aorta. In addition, 16S rRNA analysis showed that HAL also reduced diversity of the intestinal microbiota, decreased the Firmicutes-to-Bacteroidetes ratio, and increased the relative abundance of probiotics such as Akkermansia muciniphila and Lactobacillus. In the end, HAL decreased the permeability of intestine by increasing the levels of occludin and tight junction protein 1 (ZO-1) in the colon, consequently decreasing concentration of interleukin (IL)-6, IL-1 β and tumor necrosis factor-alpha (TNF- α) in serum and mRNA expressions in the aorta. Data showed that HAL alleviates AS by restraining oxidative stress, regulating intestinal microbiota, decreasing intestinal permeability and inhibiting inflammation. Our findings provided novel insights into the role and mechanism of anti-atherogenic potential of HAL. [ABSTRACT FROM AUTHOR]

Gut microbiota has been proven to play an important role in many metabolic diseases and cardiovascular disease, particularly atherosclerosis. Ophiopogonin D (OPD), one of the effective compounds in Ophiopogon japonicus, is considered beneficial to metabolic syndrome and cardiovascular diseases. In this study, we have illuminated the effect of OPD in ApoE knockout (ApoE − / −) mice on the development of atherosclerosis and gut microbiota. To investigate the potential ability of OPD to alleviate atherosclerosis, 24 eight-week-old male ApoE − / − mice (C57BL/6 background) were fed a high-fat diet (HFD) for 12 weeks, and 8 male C57BL/6 mice were fed a normal diet, serving as the control group. ApoE − / − mice were randomly divided into the model group, OPD group, and simvastatin group (n = 8). After treatment for 12 consecutive weeks, the results showed that OPD treatment significantly decreased the plaque formation and levels of serum lipid compared with those in the model group. In addition, OPD improved oral glucose tolerance and insulin resistance as well as reducing hepatocyte steatosis. Further analysis revealed that OPD might attenuate atherosclerosis through inhibiting mTOR phosphorylation and the consequent lipid metabolism signaling pathways mediated by SREBP1 and SCD1 in vivo and in vitro. Furthermore, OPD treatment led to significant structural changes in gut microbiota and fecal metabolites in HFD-fed mice and reduced the relative abundance of Erysipelotrichaceae genera associated with cholesterol metabolism. Collectively, these findings illustrate that OPD could significantly protect against atherosclerosis, which might be associated with the moderation of lipid metabolism and alterations in gut microbiota composition and fecal metabolites. [ABSTRACT FROM AUTHOR]

Baicalin is a flavonoid extracted from Scutellariae Radix and shows a variety of biological activities as reducing lipids, diminishing inflammation, and inhibiting bacterial infection. However, there is no report of baicalin against CVB3 infection. In this study, we found that baicalin can reduce viral titer in a dose-dependent manner in vitro at a dose with no direct virucidal effect. Moreover, we revealed that baicalin can also improve survival rate, reduce heart weight/body weight ratio, prevent virus replication, and relieve myocardial inflammation in the acute viral myocarditis mouse model induced by CVB3. Then, in order to explore the mechanism of baicalin inhibiting CVB3 replication, we respectively examined the expression of autophagosome marker LC3-II by Western blot, tested the concentration of free fatty acid (FFA) and cholesterol (CHO) by commercial kits, detected the mRNA levels of fatty acid synthase (Fasn) and acetyl coenzyme a carboxylase (ACC) by RT-PCR, and observed the lipid content of cells by fluorescence staining. The results showed that CVB3 infection increased autophagosome formation and lipid content in HeLa cells, but these changes were significantly blocked by baicalin. Finally, in order to confirm that baicalin inhibits viral replication and reduces autophagosome formation by reducing cellular lipids, we added exogenous palmitate to cell culture supernatants to promote intracellular lipid synthesis and found that palmitate did not alter LC3-II and CVB3/VP1 expression in HeLa cells with or without CVB3 infection. Interestingly, palmitate can reverse the inhibitory effect of baicalin on autophagosome formation and viral replication. In conclusion, our results indicated that lipids play an important role in CVB3 replication, and the effect of baicalin against CVB3 was associated with its ability to reduce cellular lipid synthesis to limit autophagosome formation. [ABSTRACT FROM AUTHOR]

Cholesterol metabolism becomes imbalanced during the formation of macrophage-derived foam cells. Pre-B-cell colony-enhancing factor (PBEF) has recently been found to affect lipid deposition and inflammation in atherosclerosis. Here, we aimed to study the effects and molecular mechanism of Polydatin on atherosclerosis in ApoE-knockout (ApoE − ∕ − ) mice. Thirty ApoE − ∕ − mice were fed a high-fat diet (HFD) for 12 weeks, and then treated with Polydatin for another 12 weeks. Whole aortas and cryosections were stained with oil red O. Blood lipid, PBEF and cytokine levels were measured by ELISA. The mRNAs of cholesterol metabolism-related genes were determined by qRT-PCR and protein levels by Western blotting. Cell cholesterol content and viability were determined in macrophages and RAW 264.7 cells. PBEF siRNA was used to study the effect of Polydatin on cholesterol metabolism in macrophages incubated with ox-LDL. Polydatin lowered blood lipids and decreased atherosclerotic lesions in ApoE − ∕ − mice. The expression of cytokines and the mRNA of cholesterol metabolism-related genes were markedly regulated by Polydatin. Meanwhile, PBEF mRNA and protein were both greatly down-regulated by Polydatin. In vitro, Polydatin protected RAW 264.7 cells treated by ox-LDL and inhibited cholesterol uptake by macrophages. The PBEF siRNA result indicates that Polydatin can modulate cholesterol metabolism in macrophages, partly through down-regulation of PBEF. In conclusion, Polydatin relieves atherosclerosis injury in ApoE − ∕ − mice, mainly through down-regulation of PBEF and inhibition of PBEF-inducing cholesterol deposits in macrophages. [ABSTRACT FROM AUTHOR]

Obesity is a significant risk factor for various diseases. It is a clinical condition caused by the excessive accumulation of fat, which has a negative impact on human health. Galactin-12 is an adipocyte-expressed protein and possesses adipocyte-inducing activity. We investigated the expression level of candidate proteins involved in galactin-12-mediated adipocyte differentiation pathway. We performed a high-throughput screening assay to monitor galectin-12 promoter activity using 105 traditional Chinese herbs. Corn silk extract and β -sitosterol reduced the expression of galactin-12 promoter in 3T3-L1 cells. In addition, corn silk extract and β -sitosterol decreased the level of lipid droplets and downregulated the gene and protein expression level of C/EBP β , C/EBP α , PPAR γ , Ap2, and adipsin in 3T3-L1 pre-adipocytes via AKT and ERK1/2 inhibition. In vivo study with the oral administration of corn silk extract and β -sitosterol in a mouse model showed a significant weight reduction and decrease in adipocytes in several organs such as the liver and adipose tissue. Taken together, corn silk extract and β -sitosterol may effectively reduce pre-adipocyte differentiation by inhibiting galectin-12 activity and exerting anti-obesity effects. These findings highlight the potential use of corn silk extract and β -sitosterol as potential candidates for the prevention and treatment of obesity. [ABSTRACT FROM AUTHOR]

Antrodia cinnamomea (AC), a protogenic fungus that only grows on the heartwood of endemic Cinnamomum kanehirae Hayata in Taiwan, is used to treat a variety of illness including liver disease. However, little is known about the benefit of AC against obesity and the related hepatic disorder. Using high-fat-diet (HFD) feed mice, we aimed to investigate whether the extract of AC (ACE) could reduce excessive weight, body fat, and serum lipids and prevent the development of non-alcoholic fatty liver (NAFLD). C57BL/6 mice were divided into five groups fed with different diets: control, HFD, and HFD with 0.5%, 1%, or 2% of ACE, respectively. After 10 weeks the animals were sacrificed, with serum and liver collected. HFD-induced elevation of body weight gain, body fat deposition, and serum free fatty acid (FFA), triacylglycerol (TGs), total cholesterol, and ratio of LDL cholesterol (LDL-C)/HDL cholesterol (HDL-C), were significantly restored by ACE. ACE reduced aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hepatic lipid deposits increased by HFD. ACE increased p-AMP activated protein kinase (pAMPK) but decreased Sterol regulatory element binding protein (SREBP), fatty acid synthase (FAS), 1-acylglycerol-3-phosphate acyltransferase (AGPAT), and 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase. The chemical analysis reveals ACE is full of triterpenes, the most abundant of which is Antcin K, followed by sulphurenic acid, eburicoic acid, antcin C, dehydrosulphurenic acid, antcin B, and propanoic acid. In conclusion, ACE should be used to prevent obesity and derived fatty liver. The applicability of ACE on NAFLD deserves further investigation. [ABSTRACT FROM AUTHOR]

Purple sweet potato leaves (PSPLs) are healthy vegetable that is rich in anti-oxidants. A solution of boiling water extract of PSPL (PSPLE) is believed to be able to prevent obesity and metabolic syndrome in the countryside of Taiwan, but its efficacy has not yet been verified. The purpose of this study was to investigate the possible anti-adipogenesis effect of PSPLE in vitro. PSPLE was used to treat the 3T3-L1 cells, and the effects on cell proliferation and adipogenesis were investigated. The results showed that PSPLE caused a dose-dependent decrease in the cell proliferation of 3T3-L1 preadipocytes, but did not alter the cell viability. In addition, PSPLE induced ERK inactivation in the 3T3-L1 preadipocytes. Furthermore, pre-treatment of confluent 3T3-L1 cells with PSPLE led to reduced lipid accumulation in differentiated 3T3-L1 cells. The inhibition of lipogenesis could result from the PSPLE-induced down-regulation of the expression of the C/EBPα and SREBP-1 transcription factors during 3T3-L1 adipocyte differentiation. These results suggest that PSPLE not only inhibits cell proliferation at an early stage but also inhibits adipogenesis at a later stage of the differentiation program. [ABSTRACT FROM AUTHOR]

The present study is to evaluate the anti-obesity effects of Eriobotrya japonica (EJ), Nelumbo nucifera (NN), and their mixture (MIX, 1:1 ratio) in 3T3-L1 adipocytes and high-fat diet-induced obese mice. The treatment of EJ, NN, and MIX in 3T3-L1 adipocytes effectively inhibited lipid accumulation, significantly decreased expression of peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element binding protein (SREBP1c), and adipocyte lipid-binding protein (aP2), and significantly increased phosphorylation of AMP-activated protein kinase (AMPK). Moreover, oral treatment of MIX showed stronger effects than individual treatment. C57BL/6J mice (6 week old) were divided into two groups; low fat diet (LFD) containing 10% calories from fat and high fat diet (HFD) containing 60% calories from fat. The HFD groups were further divided into five subgroups; treated with distilled water (HFD), treated with 400 mg/kg EJ (EJ400), treated with 400 mg/kg NN (NN400), treated with 200 mg/kg MIX (MIX200), and treated with 400 mg/kg MIX (MIX400) during 13 weeks. In our results, the administration of EJ, NN, and MIX significantly decreased body weight (BW), fat weight, liver weight, hepatic triglyceride (TG) and total cholesterol (TC), lipid droplets in the liver, food efficacy ratio, and the plasma TG, TC, glucose, insulin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in a dose-dependent manner, and MIX treatment showed stronger effect than their individual treatments. Similarly, MIX treatment decreased the expression of PPARγ, SREBP-1c, FAS, and ACC more strongly in the adipose tissue than single treatments. In conclusion, the MIX of EJ and NN extract may strongly regulate BW gain than EJ or NN alone, and its anti-obesity effect is associated with the control of lipid metabolism, including adipogenesis and lipogenesis. [ABSTRACT FROM AUTHOR]

Obesity is an important and preventable risk factor for renal disease. The administration of an antioxidant with a lipid-lowering effect is an important therapeutic approach for kidney disease in obese patients. The present study was conducted to examine whether methanolic extract of Dendrobium moniliforme (DM), one of the most famous traditional medicines used in many parts of the world, has an antioxidant effect in vitro and an ameliorative effect on high-fat diet (HFD)-induced alterations such as renal dysfunction and lipid accumulation in vivo. The 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity of DM extract (IC50 = 29.6 μg/mL) was increased in a dose-dependent manner. The LLC-PK1 kidney cell damage induced by oxidative stress was significantly inhibited by the treatments with DM extract. In the animal study, DM extract (200 mg/kg) was orally administered every day for nine weeks to HFD-fed mice, and its effect was compared with that of metformin. The administration of DM extract decreased the elevated serum glucose, total cholesterol concentration and renal lipid accumulation in HFD-fed mice. It also ameliorated renal dysfunction biomarkers including serum creatinine and renal collagen IV deposition. Taken together, these results provide important evidence that DM extract exhibits a pleiotropic effect on obesity induced parameters and exerted a renoprotective effect in HFD-fed mice. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy is a leading cause of chronic renal failure. Recently, Euonymus alatus showed therapeutic potential in the treatment of diabetes and its chronic complications. In this study, effects of Euonymus alatus and its mechanism in the treatment of diabetic nephropathy were investigated. Diabetic nephropathy was induced in Sprague-Dawley rats by uninephrectomy plus streptozotocin (STZ) administration. Euonymus alatus and irbesartan, as a positive control, were lavaged to these rats for 12 weeks. Our data showed that Euonymus alatus was efficient in lowering HbA1c, improving blood lipids, decreasing 24 h urine protein and protecting kidney function. Pathological studies found kidney damage, including extracellular matrix expansion and glomerulosclerosis, were improved by Euonymus alatus treatment. Further investigation found that the herb had a role in downregulating the expression of transform growth factor β1. In conclusion, Euonymus alatus has a protective role in diabetic nephropathy, which may be related to its downregulation of transform growth factor β1 expression. [ABSTRACT FROM AUTHOR]

The present study was conducted to determine whether lyophilized aqueous extract of alfalfa, or Medicago sativa L. could exert antioxidant activity against carbon tetrachloride-induced oxidative stress and liver injury in rats. The hepatoprotective activity of alfalfa extract was determined by assessing the levels of serum transaminases, ALP, bilirubin and lipid profile. Further, the effect of the test substance on malondialdehyde (MDA), an end product of lipid peroxidation; antioxidant liver enzyme non-protein sulfhydryl (NP-SH); and total protein (TP) were also studied. Serum transaminase, ALP, bilirubin level, lipid profile and liver MDA were significantly elevated and the antioxidant status in liver NP-SH and TP contents were declined in animals treated with 4 alone. Pretreatment with alfalfa and silymarin for three weeks prior to the administration of 4 significantly prevented the increase in the serum levels of hepatic marker, LDL, VLDL levels enzymes and reduced oxidative stress indicated by elevated NP-SH and TP concentration. The histopathological examination of the livers also showed that the alfalfa extract reduced the incidence of liver lesions induced by 4. The in vitro antioxidant assessment of alfalfa extract on DPPH and carotene-linoleic assays demonstrated a moderate antioxidant potential. Results suggest that the alfalfa extract possesses hepatoprotective and antioxidative stress properties possibly through its antioxidant phytochemical constituents and substantiates its use in various liver disorders as a hepatoprotector. [ABSTRACT FROM AUTHOR]

Polysaccharide-rich Lycium barbarum and Rehmannia glutinosa have been considered to have immune-modulating activity. This study investigated the effects of water extracted Lycium barbarum and Rehmannia glutinosa (HE) on carbon tetrachloride (CCl4)-induced liver injury in rats. Male Sprague-Dawley rats were randomly divided into: normal diet + peritoneal injection of olive oil (control), normal diet + CCl4 injection (CCl4), 1 × HE (0.05% HE for each) + CCl4 (1 × HE), and 3 × HE (0.15% HE for each) + CCl4 (3 × HE) groups. Rats were injected with 40% CCl4 at a dose of 0.75 ml/kg body weight once a week for seven weeks, one week after herbal extract treatment. After eight week herbal extract treatment, pathohistological examination showed that both 1× and 3 × HE treatments diminished necrotic hepatocytes, chemoattraction of inflammatory cells, and liver fibrosis. Both 1× and 3 × HE treatments decreased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and reduced hepatic levels of pro-inflammatory cytokines - tumor necrosis factor-α and interleukin-1β - compared to CCl4 treatment alone. The 1 × HE treatment increased hepatic anti-inflammatory cytokine IL-10 levels. Both the 1× and 3 × HE treatments suppressed liver fibrosis biomarkers - transforming growth factor-β1 and hydroxyproline. Therefore, treatment with water extracted Lycium barbarum and Rehmannia glutinosa (0.05% and 0.15% for each) for eight weeks protects against necrotic damage, indicated by decreases in plasma ALT and AST activities, and suppresses liver fibrosis by down-regulation of liver inflammation in rats with CCl4-induced liver injury. [ABSTRACT FROM AUTHOR]

Rhizoma Arisaematis (RA, the rhizome of Pinellia pedatisecta Schott) is a traditional Chinese medicine commonly used in the treatment of convulsions, inflammation, and cancer. Despite the fact that it has been used for more than 2000 years, the pharmacological and toxic effects of traditionally processed products of RA are still unclear. In this study, we attempted to investigate the effects exerted by untreated crude RA and different preparations of RA treated with alumen in combination with ginger juice (Zhinanxing) or bile juice (Dannanxing) in ICR mice. The results showed that both the Zhinanxing and Dannanxing water extracts exerted significantly increased sedative effects, as indicated by the inhibitory effects on ambulatory distances, jumps, vertical-plane entries, and prolonged pentobarbital-induced sleeping time. The extracts also exerted significantly increased analgesic effects (increase of tail flick latency in nociceptive testing) in mice than did the unprocessed crude RA after oral administration for one to three days, and effects persisted 18 days after the cessation of treatment. By contrast, the toxic effects, such as an increase in stereotype-1 episodes of locomotor activities and reduction of the retention time on a rotating rod (motor equilibrium dysfunction), were observed only in mice treated with the unprocessed crude RA for three consecutive days, and effects persisted for 18 days after the cessation of treatment. These neurotoxic effects were accompanied by an increase in plasma lipid peroxidation (LPO), decrease in whole blood nitric oxide (NOx) levels, and inhibition of Na+/K+-ATPase activities in membrane fractions of erythrocytes and in the cerebral cortex. In conclusion, these findings provide scientific evidence that the processed RA indeed possesses not only enhanced neuropharmacological efficacy but also reduced neurotoxic effects as compared to the unprocessed crude RA. The signaling of NOx/oxidative stress/Na+-K+- ATPase activities played a role, at least in part, in the underlying mechanisms of neurotoxic effects induced by the crude RA. [ABSTRACT FROM AUTHOR]