Mulberry leaf extract inhibits obesity and protects against diethylnitrosamine-induced hepatocellular carcinoma in rats.

Mulberry leaf has been recognized as a traditional Chinese medicinal plant, which was distributed throughout the Asia. The aqueous extract of mulberry leaf extract (MLE) has various biologically active components such as polyphenols and flavonoids. However, the inhibitory effect of MLE in hepatocarcinogenesis is poorly understood. In this study, we determined the role of MLE supplementation in preventing hepatocarcinogenesis in a carcinogen-initiated high-fat diet (HFD)-promoted Sprague-Dawley (SD) rat model. The rats were fed an HFD to induce obesity and spontaneous hepatomas by administering 0.01% diethylnitrosamine (DEN) in their drinking water for 12 weeks (HD group), and also to fed MLE through oral ingestion at daily doses of 0.5%, 1%, or 2%. At the end of the 12-week experimental period, the liver tumors were analyzed to identify markers of oxidative stress and antioxidant enzyme activities, and their serum was analyzed to determine their nutritional status and liver function. Histopathological analysis revealed that MLE supplementation significantly suppressed the severity and incidence of hepatic tumors. Furthermore, compared with the HFD + DEN groups, the expression of protein kinase C (PKC)-α and Rac family small GTPase 1 (Rac1) was lower in the MLE groups. These findings suggest that MLE prevents obesity-enhanced, carcinogen-induced hepatocellular carcinoma development, potentially through the protein kinase C (PKC)α/Rac1 signaling pathway. MLE might be an effective chemoprevention modality for nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH)-related hepatocarcinogenesis.

Improving the Effects of Mulberry Leaves and Neochlorogenic Acid on Glucotoxicity-Induced Hepatic Steatosis in High Fat Diet Treated db/db Mice.

There are many complications of type 2 diabetes mellitus. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are two complications related to the increased lipid accumulation in the liver. Previous studies have shown that mulberry leaf water extract (MLE) has the effect of lowering lipid levels in peripheral blood, inhibiting the expression of fatty acid synthase (FASN) and increasing the activity of liver antioxidant enzymes superoxide dismutase (SOD) and catalase. Our study aimed to investigate the role of MLE and its main component, neochlorogenic acid (nCGA), in reducing serum lipid profiles, decreasing lipid deposition in the liver, and improving steatohepatitis levels. We evaluated the antioxidant activity including glutathione (GSH), glutathione reductase (GRd), glutathione peroxidase (GPx), glutathione S-transferase (GST), and superoxide dismutase (SOD), and catalase was tested in mice fed with MLE and nCGA. The results showed a serum lipid profile, and fatty liver scores were significantly increased in the HFD group compared to the db/m and db mice groups, while liver antioxidant activity significantly decreased in the HFD group. When fed with HFD + MLE or nCGA, there was a significant improvement in serum lipid profiles, liver fatty deposition conditions, steatohepatitis levels, and liver antioxidant activity compared to the HFD group. Although MLE and nCGA do not directly affect the blood sugar level of db/db mice, they do regulate abnormalities in lipid metabolism. These results demonstrate the potential of MLE/nCGA as a treatment against glucotoxicity-induced diabetic fatty liver disease in animal models.

Nelumbo nucifera leaves extract ameliorated scopolamine-induced cognition impairment via enhanced adult hippocampus neurogenesis.

In this presentation, we explored the molecular mechanisms of N. nucifera leaf water extracts (NLWEs) and polyphenol extract (NLPE) on scopolamine-induced cell apoptosis and cognition defects. The administration of NLWE and NLPE did not alter the body weight and serum biomarker rs and significantly ameliorated scopolamine-induced cognition impairment according to Y-maze test analysis. In mice, treatment with scopolamine disrupted normal histoarchitecture in the hippocampus, whereas the administration of NLWE and NLPE reversed the phenomenon. Western blot analysis revealed that scopolamine mitigated the expression of doublecortin (DCX), nestin, and NeuN, and cotreatment with NLWE or NLPE significantly recovered the expression of these proteins. NLWE and NLPE upregulated DCX and NeuN expression in the hippocampus region, as evidenced by immunohistochemical staining analysis of scopolamine-treated mice. NLWE and NLPE obviously elevated brain-derived neurotrophic factor (BDNF) and enhanced its downstream proteins activity. NLWE and NLPE attenuated scopolamine-induced apoptosis by reducing Bax and increased Bcl-2 expression. In addition, scopolamine also triggered apoptosis in human neuroblastoma SH-SY5Y cells whereas co-treatment with NLWE or quercetin-3-glucuronide (Q3G) reversed the phenomenon. NLWE or Q3G enhanced Bcl-2 and reduced Bax expression in the presence of scopolamine in SH-SY5Y cells. NLWE or Q3G recovered the inhibitory effects of scopolamine on neurogenesis and BDNF signals in SH-SY5Y cells. Overall, our results revealed that N. nucifera leaf extracts and Q3G promoted adult hippocampus neurogenesis and prevented apoptosis to mitigate scopolamine-induced cognition dysfunction through the regulation of BDNF signaling pathway.

Quercetin-3-O-ß-d-glucuronide in the Nuciferine Leaf Polyphenol Extract Promotes Neurogenesis Involving the Upregulation of the Tropomyosin Receptor Kinase (Trk) Receptor and AKT/Phosphoinositide 3-Kinase Signaling Pathway.

Neurogenesis is crucial during the human lifespan for the maintenance of synaptic plasticity and normal function. The impairment of hippocampal neurogenesis in adults may lead to neurodegenerative disease, such as Alzheimer's disease. Miquelianin (quercetin-3-O-ß-d-glucuronide, Q3GA) is a constituent of the nuciferine leaf polyphenol extract (NLPE), and it has protective effects against neurodegeneration. In this study, we examined the effect of the NLPE on neurogenesis and the mechanisms underlying Q3GA on neurogenesis. We fed 24-week-old male C57BL/6 mice with 0.1 or 0.25% NLPE for 2 weeks. NLPE treatment increased small spindle-shaped stem cell numbers in the subgranular zone and the number of doublecortin (DCX)- and neuron-specific nuclear protein (NeuN)-expressing neurons. HT22, a hippocampal cell line, treated with Q3GA revealed significant neurite growth and upregulated TrkR and PI3K/Akt levels. The evidence from a model of retinoic acid-induced SH-SY5Y cell differentiation showed that Q3GA or NLPE increases neurite growth significantly. Taken together, the NLPE containing Q3GA to promote neurogenesis involving the upregulation of TrkR and the PI3K/Akt signaling pathway might be potentiated as an alternative strategy for the treatment of neurodegeneration.

Mulberry leaf extract and neochlorogenic acid ameliorate glucolipotoxicity-induced diabetic nephropathy in high-fat diet-fed db/db mice.

Diabetic nephropathy, a major diabetes complication, is often exacerbated by glucolipotoxicity. The potential benefits of mulberry leaf extract (MLE) and its primary component, neochlorogenic acid (nCGA), in combating this condition have not been extensively explored. High-fat diet-fed db/db mice were employed as a model for glucolipotoxicity-induced diabetic nephropathy. The mice were treated with MLE or nCGA, and their body weight, insulin sensitivity, blood lipid profiles, and kidney function were assessed. In addition, modulation of the JAK-STAT, pAKT, Ras, and NF-κB signaling pathways by MLE and nCGA was evaluated. MLE and nCGA did not significantly decrease blood glucose level but effectively mitigated the adverse effects of a high-fat diet on blood lipid profile and kidney function. Improvements in body weight, insulin sensitivity, and kidney structure, along with a reduction in fibrosis, were observed. Both MLE and nCGA regulated lipid metabolism abnormalities, significantly inhibited the accumulation of glycosylated substances in glomeruli, and modulated crucial signaling pathways involved in diabetic nephropathy. Although they do not directly affect blood glucose level, MLE and nCGA show significant potential in managing glucolipotoxicity-induced diabetic nephropathy by targeting lipid metabolism and key molecular pathways. The present findings suggest MLE and nCGA may be promising therapeutic agents for diabetic nephropathy, and further exploration in human patients is warranted.

Acarbose Protects Glucolipotoxicity-Induced Diabetic Nephropathy by Inhibiting Ras Expression in High-Fat Diet-Fed db/db Mice.

Diabetic nephropathy (DN) exacerbates renal tissue damage and is a major cause of end-stage renal disease. Reactive oxygen species play a vital role in hyperglycemia-induced renal injury. This study examined whether the oral hypoglycemic drug acarbose (Ab) could attenuate the progression of DN in type 2 diabetes mellitus mice. In this study, 50 mg/kg body weight of Ab was administered to high-fat diet (HFD)-fed db/db mice. Their body weight was recorded every week, and the serum glucose concentration was monitored every 2 weeks. Following their euthanasia, the kidneys of mice were analyzed through hematoxylin and eosin, periodic acid Schiff, Masson's trichrome, and immunohistochemistry (IHC) staining. The results revealed that Ab stabilized the plasma glucose and indirectly improved the insulin sensitivity and renal functional biomarkers in diabetic mice. In addition, diabetes-induced glomerular hypertrophy, the saccharide accumulation, and formation of collagen fiber were reduced in diabetic mice receiving Ab. Although the dosages of Ab cannot decrease the blood sugar in db/db mice, our results indicate that Ab alleviates glucolipotoxicity-induced DN by inhibiting kidney fibrosis-related proteins through the Ras/ERK pathway.

Gallic Acid Improves Diabetic Steatosis by Downregulating MicroRNA-34a-5p through Targeting NFE2L2 Expression in High-Fat Diet-Fed db/db Mice.

Type 2 diabetes mellitus (T2DM) has become epidemic worldwide and is strongly associated with nonalcoholic fatty liver disease (NAFLD). The molecular mechanisms of microRNAs in NAFLD and T2DM development and the corresponding therapies remain unclear. We performed microRNA microarray validation to determine whether hepatic miR-34a-5p was significantly upregulated in db/db mice fed with a high-fat diet (HFD), a mouse model of T2DM with steatohepatitis. The potential role of miR-34a-5p and gallic acid (GA) in regulating hepatic lipid metabolism and diabetic steatosis was explored. GA improved the activities of antioxidant enzymes and suppressed lipid accumulation in the HFD-induced steatotic liver of db/db mice. In vitro, the silencing of miR-34a-5p in hepatocyte HepG2 cells ameliorated high glucose + oleic acid/palmitic acid mixture-induced accumulation of cellular triglycerides. We identified nuclear factor erythroid-derived 2-like 2 (NFE2L2) as a direct target of miR-34a-5p. Reduction in intracellular triglyceride and the expression levels of sterol regulatory element-binding protein 1 and fatty acid synthase by GA were mediated by the inhibition of miR-34a-5p expression in HepG2 cells. The findings suggest that GA improves hepatic lipogenesis by downregulating miR-34a-5p by suppressing NFE2L2 expression, indicating the potential therapeutic role of GA or an NFE2L2-activating agent in diabetic fatty liver disease.

Nelumbo nucifera leaf polyphenol extract and gallic acid inhibit TNF-α-induced vascular smooth muscle cell proliferation and migration involving the regulation of miR-21, miR-143 and miR-145.

Nelumbo nucifera leaf water extract (NLE) attenuates high-fat diet (HFD)-induced rabbit atherosclerosis, but its mechanism of action and the relevant compounds remain unclear. Modulating the proliferation and migration of vascular smooth muscle cells (VSMCs) may be an enforceable strategy for atherosclerosis prevention. Therefore, we investigated the potential mechanisms of N. nucifera leaf polyphenol extract (NLPE) and its active ingredient gallic acid (GA) in VSMC proliferation and migration. A7r5 rat aortic VSMCs were provoked using 50 ng mL-1 tumor necrosis factor (TNF)-α; the NLPE or GA reduced the TNF-α-induced migration by inhibiting the transforming protein RhoA/cell division cycle protein 42 pathway. The NLPE or GA suppressed the TNF-α-induced VSMC proliferation by inhibiting the Ras pathway and increasing the expression of phosphatase and tensin homolog (PTEN), kinase suppressor of Ras 2, and inducible nitric oxide synthase. The NLPE or GA increased PTEN expression by downregulating microRNA (miR)-21 expression and reduced Ras and RhoA expression by upregulating miR-143 and miR-145 expression. The NLPE and GA use potentially prevents atherosclerosis by inhibiting the VSMC migration and proliferation. The mechanisms involve the regulation of the miRNA in PTEN, the Ras/extracellular-signal-regulated kinase pathway, and Rho family proteins.

Inhibitory Effect of Nelumbo nucifera Leaf Extract on 2-Acetylaminofluorene-induced Hepatocarcinogenesis Through Enhancing Antioxidative Potential and Alleviating Inflammation in Rats.

Leaf extract of Nelumbo nucifera (NLE) has been demonstrated to possess anti-atherosclerosis, improve alcohol-induced steatohepatitis, prevent high-fat diet-induced obesity, and inhibit the proliferation and metastasis of human breast cancer cells. This study determines the chemopreventive role of NLE against 2-acetylaminofluorene (AAF)-induced hepatocellular carcinoma (HCC) in rats. AAF was used to induce hepatocarcinogenesis in rats through genetic and nongenetic effects. After administration for 12 weeks, NLE (0.5-2%) supplementation orally inhibited AAF (0.03%)-induced hepatic fibrosis which appears during the development of premalignant lesions in rats. After the 6-month experiment, NLE supplementation resulted in decreasing AAF-induced serum parameters of hepatic injury, including the level of triglycerides, total cholesterol, alpha-fetoprotein (AFP), and inflammatory mediator interleukin (IL)-6 and tumor necrosis factor (TNF)-α as well as the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (γGT). NLE supplementation also reduced AAF-induced lipid peroxidation and 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in the rat liver. Hepatic histopathological investigation revealed that NLE supplementation attenuated the AAF-induced HCC and glutathione S-transferase-Pi (GST-Pi) expression. Furthermore, NLE supplementation increased the expression of transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream targets, including catalase, glutathion peroxidase (GPx), and superoxide dismutase 1 (SOD-1) in the rat liver. Our findings indicate that NLE supplementation inhibited AAF-induced hepatocarcinogenesis by enhancing antioxidative potential and alleviating inflammation in rats.

Nelumbo nucifera leaves extract attenuate the pathological progression of diabetic nephropathy in high-fat diet-fed and streptozotocin-induced diabetic rats.

Diabetic nephropathy is not only a common and severe microvascular complication of diabetes mellitus but also the leading cause of renal failure. Lotus (Nelumbo nucifera) possesses antioxidative and anticancer properties. The present study aimed to investigate the antidiabetic and renoprotective effects of N. nucifera leaf extract (NLE) in a rat model of type 2 diabetic mellitus. Male Sprague-Dawley rats with type 2 diabetes induced by a high-fat diet (HFD)/streptozotocin (STZ) were treated with NLE at dosages of 0.5% and 1% (w/w) daily for 6 weeks. At the end of the experimental period, body weight, serum glucose levels, insulin levels, and kidney function were assessed. Furthermore, antioxidant enzyme and lipid peroxide levels were determined in the kidney, and histopathological examination was performed using hematoxylin and eosin staining, periodic acid Schiff staining, and Masson trichrome staining. To shed light on the molecular mechanism underlying the functioning of NLE, mouse glomerular mesangial cells (MES-13) treated with high glucose (HG, 25 mM glucose) were chosen as a model for an examination of the signal transduction pathway of NLE. The results revealed that NLE improved diabetic kidney injury by reducing blood glucose, serum creatinine, and blood urea nitrogen levels and enhanced antioxidant enzyme activities in kidney tissue. Treatment with NLE significantly reduced the malondialdehyde and 8-hydroxy-2-deoxyguanosine levels and increased serum insulin levels; expression of renal superoxide dismutase, catalase, and glutathione peroxidase activities; and glutathione content. Histological studies have also demonstrated that NLE treatment inhibited the dilation of Bowman's capsule, which confirmed its renoprotective action in diabetes. In addition, treatment with NLE and its major component quercetin 3-glucuronide attenuated 25 mM HG-induced suppressed nuclear factor erythroid 2-related factor 2 and antioxidant enzyme expression in MES-13 cells. Collectively, these findings indicate that NLE may have antidiabetic and renoprotective effects against HFD/STZ-induced diabetes, at least in part, through antioxidative pathways.

Endoplasmic Reticulum Stress-Induced Resistance to Doxorubicin Is Reversed by Mulberry Leaf Polyphenol Extract in Hepatocellular Carcinoma through Inhibition of COX-2.

Mulberry (Morus alba L.) leaves are used in Chinese medicine to treat metabolic disorders. Mulberry leaf polyphenol extracts (MLPE) have recently been shown to exhibit anticancer properties. Endoplasmic reticulum (ER) stress represents a pivotal obstacle in solid tumors, resulting in the antiapoptosis of tumor cells and drug resistance. In this study, pretreatment with the ER stress inducer tunicamycin (TM) attenuated the percentage of apoptosis induced by doxorubicin (DOX). Cotreatment with tunicamycin and MLPE reversed apoptosis induced by DOX. Simultaneously, induction of ER stress with tunicamycin resulted in an increased expression of Cyclooxygenase 2 (COX-2) and Glucose-regulated protein (GRP78) concomitant with the activation of p38 MAPK/PI3K/Akt in HepG2 cells. Furthermore, the suppression of ER stress with celecoxib or p38 MAPK inhibitor successfully recovered DOX-induced apoptosis. Consistent with the inhibition of COX-2 or p38 MAPK, copretreatment with TM and MLPE drastically recovered cytotoxicity and caspase-3 activation in the presence of DOX. These results reveal that MLPE reduces ER stress-induced resistance to DOX in hepatocellular carcinoma (HCC) cells through downregulation of COX-2- or p38 MAPK-mediated PI3K/Akt pathway.

Nelumbo nucifera leaf extract treatment attenuated preneoplastic lesions and oxidative stress in the livers of diethylnitrosamine-treated rats.

Lotus (Nelumbo nucifera Gaertn) possesses antioxidant, hepatoprotective, and anticancer potential. This study determined the protective role of aqueous extract from Nelumbo nucifera leaves (NLE) against N-diethylnitrosamine (DEN)-induced oxidative stress and hepatocellular carcinogenesis in a sample of Sprague-Dawley rats. NLE was fed orally to rats in which hepatic carcinoma was induced with DEN for 12 weeks. Five groups of 12 rats each were used for the study: Group I (control group) rats received distilled water; Group II rats were induced with DEN; Group III rats were induced with DEN and cotreated with 0.5% NLE; Group IV rats were induced with DEN and cotreated with 1.0% NLE; and Group V rats were induced with DEN and cotreated with 2.0% NLE. Clinical chemistry, organ weight, inflammatory marker, protein expression, enzyme, and antioxidant analyses were conducted. NLE administration to rats resulted in significantly decreased levels of serum alanine aminotransferase, aspartate aminotransferase, and albumin, which is indicative of hepatocellular damage, compared with the control group. DEN-induced oxidative stress was inhibited by NLE and this inhibition was paralleled by decreased lipid peroxides and increased glutathione transferase, superoxide dismutase, catalase, and glutathione peroxidase activity in liver tissues. The status of nonenzymatic antioxidants, such as reduced glutathione, was also found to be increased in NLE-administered rats. Furthermore, NLE decreased tumor size, hepatic Rac1, PKCα, and GSTπ expressions compared with the DEN-only group. Thus, supplementation of NLE reduced the adverse changes that occur because of liver cancer. These results prove that NLE protects against liver carcinogenesis induced because of treatment with DEN through blocking lipid peroxidation, hepatic cell damage, and enhancing the antioxidant defense system.

Antrodia cinnamomea Prevents Obesity, Dyslipidemia, and the Derived Fatty Liver via Regulating AMPK and SREBP Signaling.

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.

Solanum nigrum Suppress Angiogenesis-Mediated Tumor Growth Through Inhibition of the AKT/mTOR Pathway.

Solanum nigrum L., an edible plant and local dish, has been assigned anticancer activities. However, the anticancer mechanisms of S. nigrum are poorly understood. Here, we investigated whether the water or polyphenol extracts of S. nigrum (SNWE or SNPE) could inhibit angiogenesis-mediated tumor growth. In nude mice bearing tumor xenografts, SNWE or SNPE significantly reduced the volume and weight of the tumors, and decreased the expression of CD31, a marker for angiogenesis. SNWE or SNPE was found to inhibit the VEGF-induced capillary structure formation of endothelial cells. The chicken egg chorioallantoic membrane (CAM) and matrigel plug assays showed further that SNWE or SNPE inhibited tumor angiogenesis. In human umbilical vascular endothelial cells (HUVECs), SNWE or SNPE suppressed the VEGF-induced activation of AKT and mTOR. Moreover, SNWE or SNPE inhibited the viability of human hepatoma HepG2 cells, and these effects were correlated with the extent of inhibition of the AKT/mTOR pathway. Taken together, our data imply that SNWE or SNPE downregulated the AKT/mTOR pathway in HUVECs and HepG2 cells, which lead to reduced tumor growth and angiogenesis.

Nelumbo nucifera Gaertn leaves extract inhibits the angiogenesis and metastasis of breast cancer cells by downregulation connective tissue growth factor (CTGF) mediated PI3K/AKT/ERK signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Nelumbo nucifera Gaertn (Nymphaeaceae) has been recognized as a medicinal plant, which was distributed throughout the Asia. The aqueous extract of Nelumbo nucifera leaves extract (NLE) has various biologically active components such as polyphenols, flavonoids, oligomeric procyanidines. However, the role of NLE in breast cancer therapy is poorly understood. THE AIM OF THIS STUDY: The purpose of this study was to identify the hypothesis that NLE can suppress tumor angiogenesis and metastasis through CTGF (connective tissue growth factor), which has been implicated in tumor angiogenesis and progression in breast cancer MDA-MB-231 cells. RESULTS: We examined the effects of NLE on angiogenesis in the chicken chorioallantoic membrane (CAM) model. The data showed that NLE could reduce the chorionic plexus at day 17 in CAM and the duration of this inhibition was dose-dependent. In Xenograft model, NLE treatment significantly reduced tumor weight and CD31 (capillary density) over control, respectively. We examined the role of angiogenesis involved restructuring of endothelium using human umbilical vein endothelial cell (HUVEC) in Matrigel angiogenesis model. The results indicated that vascular-like structure formation was further blocked by NLE treatment. Moreover, knockdown of CTGF expression markedly reduced the expression of MMP2 as well as VEGF, and attenuated PI3K-AKT-ERK activation, indication that these signaling pathways are crucial in mediating CTGF function. CONCLUSION: The present results suggest that NLE might be useful for treatment in therapy-resistance triple negative breast cancer.

Polyphenolic extract from Hibiscus sabdariffa reduces body fat by inhibiting hepatic lipogenesis and preadipocyte adipogenesis.

Diets high in fat lead to excess lipid accumulation in adipose tissue, which is a crucial factor in the development of obesity, hepatitis, and hyperlipidemia. In this study, we investigated the anti-obesity effect of Hibiscus sabdariffa extract (HSE) in vivo. Hamsters fed a high-fat diet (HFD) develop symptoms of obesity, which were determined based on body weight changes and changes in plasma and serum triglycerides, free fatty acid concentrations, total cholesterol levels, LDL-C levels, HDL-C levels, and adipocyte tissue weight. HFD-fed hamsters were used to investigate the effects of HSE on symptoms of obesity such as adipogenesis and fatty liver, loss of blood glucose regulation, and serum ion imbalance. Interestingly, HSE treatment effectively reduced the effects of the HFD in hamsters in a dose-dependent manner. Further, after inducing maturation of preadipocytes, Hibiscus sabdariffa polyphenolic extract (HPE) was shown to suppress the adipogenesis of adipocytes. However, HPE does not affect the viability of preadipocytes. Therefore, both HSE and HPE are effective and viable treatment strategies for preventing the development and treating the symptoms of obesity.

Sechium edule Shoot Extracts and Active Components Improve Obesity and a Fatty Liver That Involved Reducing Hepatic Lipogenesis and Adipogenesis in High-Fat-Diet-Fed Rats.

Excess fat accumulation in the liver increases the risk of developing progressive liver injuries ranging from a fatty liver to hepatocarcinoma. In a previous study, we demonstrated that the polyphenol components of Sechium edule shoots attenuated hepatic lipid accumulation in vitro. Therefore, we investigated the effects and mechanisms of the extract of S. edule shoots (SWE) to modulate fat accumulation in a high-fat-diet (HFD)-induced animal model. In this study, we found that the SWE can reduce the body weight, adipose tissue fat, and regulate hepatic lipid contents (e.g., triglyceride and cholesterol). Additionally, treatment of caffeic acid (CA) and hesperetin (HPT), the main ingredients of SWE, also inhibited oleic acid (OA)-induced lipid accumulation in HepG2 cells. SWE enhanced the activation of AMP-activating protein kinase (AMPK) and decreased numerous lipogenic-related enzymes, such as sterol regulator element-binding proteins (SREBPs), e.g., SREBP-1 and SREBP-2, and HMG-CoA reductase (HMGCoR) proteins, which are critical regulators of hepatic lipid metabolism. Taken together, the results demonstrated that SWE can prevent a fatty liver and attenuate adipose tissue fat by inhibiting lipogenic enzymes and stimulating lipolysis via upregulating AMPK. It was also demonstrated that the main activation components of SWE are both CA and HPT.

Luteolin enhances paclitaxel-induced apoptosis in human breast cancer MDA-MB-231 cells by blocking STAT3.

The potential use of low-dose chemotherapy has been appealing because lower dosages are more attainable during cancer therapy and cause less toxicity in patients. Combination therapy of paclitaxel, a promising frontline chemotherapy agent, with natural anti-tumor agents that are considerably less toxic and possess the capability of activating additional apoptotic signals may provide a rational molecular basis for novel chemotherapeutic strategies. Luteolin, a natural flavone, possesses multiple biological activities, including anti-tumor potential. In the present study, the effects of concomitant administration of luteolin and paclitaxel were investigated in human breast cancer MDA-MB-231 cells. Luteolin alone demonstrated an anti-proliferative effect. Co-administration of luteolin and paclitaxel resulted in an increase in apoptosis compared with the treatment of paclitaxel alone as evidenced by the results of a diamidino-2-phenylindole (DAPI) stain and Annexin-V-based assay. Moreover, immunoblotting analysis also showed that the co-administration of luteolin and paclitaxel activated caspase-8 and caspase-3 and increased the expression of Fas. Furthermore, the increased expression of Fas due to co-administration was shown to be due to the blocking of signal transducer and activator of transcription 3 (STAT3). Finally, combination therapy with luteolin and paclitaxel significantly reduced tumor size and tumor weight in an orthotopic tumor model of MDA-MB-231 cells in nude mice. These results suggest that the luteolin-paclitaxel combination could be a novel strategy for the treatment of breast cancer.

The polyphenol extract from Sechium edule shoots inhibits lipogenesis and stimulates lipolysis via activation of AMPK signals in HepG2 cells.

Fatty liver may have implications for metabolic syndrome, such as obesity, hypertension, and diabetes. Therefore, the development of pharmacological or natural agents to reduce fat accumulation in the liver is an important effort. The Sechium edule shoots have already been verified to decrease serum lipids and cholesterol and prevent atherosclerosis. However, how Sechium edule shoots modulate hepatic lipid metabolism is unclear. This study was designed to investigate the effects and mechanisms of polyphenol extracts (SPE) of Sechium edule shoots in reducing lipid accumulation in oleic acid-treated HepG2 cells. We found that water extracts (SWE) of Sechium edule shoots could decrease serum and hepatic lipid contents (e.g., triacylglycerol and cholesterol). Furthermore, SWE and SPE through the AMPK (AMP-activating protein kinase) signaling pathway could decrease lipogenic relative enzymes, such as FAS (fatty acid synthase), HMGCoR (HMG-CoA reductase), and SREBPs (sterol regulatory element binding proteins), and increase the expression of CPT-I (carnitine palmitoyltransferase I) and PPARα (peroxisome proliferators activated receptor α), which are critical regulators of hepatic lipid metabolism. These observations suggested that Sechium edule shoots have potential for developing health foods for preventing and remedying fatty liver.

Mulberry leaf extract inhibits the development of atherosclerosis in cholesterol-fed rabbits and in cultured aortic vascular smooth muscle cells.

This study used high-cholesterol-fed New Zealand white rabbits and aortic vascular smooth muscle cells (VSMCs) to investigate the impact of mulberry leaf extract (MLE) on the development of atherosclerosis. The results show that the major components of MLE are polyphenols, flavonoids, carbohydrates, proteins, and lipids, and the major contituents of mulberry leaf polyphenol extract (MLPE) are polyphenols and flavonoids. In addition to improvement of liver function, the atheroma burden and levels of serum cholesterol, triglycerides, and low-density lipoprotein (LDL) are also significantly reduced after MLE treatment. MLE and MLPE improved endothelial function, inhibited proliferation and migration of aortic VSMCs, and reduced atheromas in the vascular wall. In conclusion, this study demonstrates that, in addition to exerting hypolipidemic effects, MLE and MLPE can effectively inhibit proliferation and migration of aortic VSMCs, improve vascular endothelial function, and reduce atheroma burden, thereby preventing atherosclerosis.