Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver diseases associated with unfavorable metabolic profiles and oxidative stress parameters. This study was designed to determine the effects of purslane seeds consumption with a low-calorie diet on insulin resistance, lipid profile, and oxidative stress indices in patients with NAFLD. This randomized controlled clinical trial was conducted on 54 individuals with NAFLD. Subjects were randomly assigned to consume either 10 g/day of purslane seeds sachet before breakfast and dinner in addition to a low-calorie diet (n = 27) or only the low-calorie diet (n = 27) for 8 weeks. Fasting blood samples were collected at the beginning and end of the study to measure relevant variables. Intake of purslane seeds with the low-calorie diet led to a significant decrease in serum concentrations of fasting blood sugar (FBS; -3.52 ± 10.45 compared with 3.03 ± 9.01 mg/dl, P = 0.017), quantitative insulin sensitivity check index (QUICKI; 0.13 ± 0.27 compared with -0.002 ± 0.016, P = 0.017), total cholesterol (4.33 ± 34.04 compared with 23.48 ± 29.47 mg/dl, P = 0.032), and low-density lipoprotein cholesterol (LDL-C; -4.35 ± 22.65 compared with 11.82 ± 16.08 mg/dl, P = 0.004) after intervention. Compared with the control group, purslane seeds consumption with adherence to a low-calorie diet had beneficial effects on FBS, HOMA-IR, QUICKI, serum total, and LDL-C in patients with NAFLD but did not affect other glycemic, lipid profile, and oxidative stress parameters.

Evidence suggests that auranofin (AF) exhibits anticancer activity by inhibiting thioredoxin reductase (TrxR). Here, in this study, we have investigated the synergistic effects of AF and morin and their mechanism for the anticancer effects focusing on apoptosis in Hep3B human hepatocellular carcinoma cells. We assessed the anticancer activities by annexin V/PI double staining, caspase, and TrxR activity assay. Morin enhances the inhibitory effects on TrxR activity of AF as well as reducing cell viability. Annexin V/PI double staining revealed that morin/AF cotreatment induced apoptotic cell death. Morin enhances AF-induced mitochondrial membrane potential (ΔΨm) loss and cytochrome c release. Further, morin/AF cotreatment upregulated death receptor DR4/DR5, modulated Bcl-2 family members (upregulation of Bax and downregulation of Bcl-2), and activated caspase-3, -8, and -9. Morin also enhances AF-induced reactive oxygen species (ROS) generation. The anticancer effects results from caspase-dependent apoptosis, which was triggered via extrinsic pathway by upregulating TRAIL receptors (DR4/DR5) and enhanced via intrinsic pathway by modulating Bcl-2 and inhibitor of apoptosis protein family members. These are related to ROS generation. In conclusion, this study provides evidence that morin can enhance the anticancer activity of AF in Hep3B human hepatocellular carcinoma cells, indicating that its combination could be an alternative treatment strategy for the hepatocellular carcinoma.

This study was performed to study the in vitro and in vivo efficacy of hydroalcoholic extract of curry leaf (CLE) rich in carbazole alkaloids, against LPS-induced inflammation in Raw 264.7 macrophages and cerulein-induced acute pancreatitis, respectively. CLE was characterized by Fourier-transform infrared (FTIR) and liquid chromatography-mass spectrometry. Raw 264.7 cells were stimulated with LPS (2 μg/ml) and treated with CLE. The animals were treated with two doses of CLE (100 and 300 mg/kg). Plasma biochemistry, tissue lipid peroxidation, cytokines, and histological examination were evaluated. CLE was found to decently scavenge the activity of DPPH radical. It dose dependently suppressed nitrite production and oxidative stress in macrophages. CLE alleviated LPS-induced inflammation in macrophages as evident from the results of various inflammatory cytokines (IL-1β, IL-6, and TNF-α). In vivo, CLE reduced cerulein-induced pancreatic edema. CLE significantly abrogated the cerulein-induced lipid peroxidation, nitrite, MPO, and GSH levels. The inflammatory cytokines and p65-NFκB activity were significantly reduced by CLE. Mechanistically, CLE reduced the expression of NT, MPO, IL-1β, ICAM-1, and COX-2, and increased the expression of Nrf2. It reduced distant organ damage markers as well. We report for the first time that CLE holds substantial potential for the prevention of acute pancreatitis.

Improvement of bone formation is necessary for successful treatment of the bone defects associated with osteoporosis. In this study, we sought to elucidate the osteogenic activity of peanut sprouts and their bioactive components. We found that peanut sprout water extract (PSWE) enhanced bone morphogenetic protein-2-mediated osteoblast differentiation in a dose-dependent manner by stimulating expression of runt-related transcription factor 2 (Runx2) via activation of AKT/MAP kinases. We identified a major component of PSWE, soyasaponin Bb, as the bioactive compound responsible for improvement of anabolic activity. Soyasaponin Bb from PSWE enhanced expression of the osteogenic transcription factor Runx2 and alkaline phosphatase. The soyasaponin Bb content depended on sprouting time of peanut, and the anabolic action of PSWE was dependent on soyasaponin Bb content. Thus, PSWE and soyasaponin Bb have the potential to protect against bone disorders, including osteoporosis.

Pomegranate is rich in tannins, polyphenols, flavonoids, and several other types of antioxidant compounds whose role in weight loss has been shown in previous studies. However, the results have been mixed regarding the effects of pomegranate consumption on weight loss. Electronic databases such as PubMed, Scopus, ISI Web of Science, and Google Scholar were systematically searched up to May 2018 for controlled clinical trials assessing the effect of pomegranate consumption on weight loss. A random effects model was used to calculate the weighted mean difference (WMD) and 95% confidence interval (CI) as the difference between the mean for the intervention and control groups. Thirteen randomized controlled trials (including 513 participants) were included in the present meta-analysis. Compared with the control groups, there was no significant reduction in bodyweight, body mass index, waist circumference, and body fat percentage after pomegranate consumption (WMD = -0.23 kg, 95% CI: -0.94, 0.47, P = 0.515; WMD = -0.12 kg/m2 , 95% CI: -0.29, 0.03, P = 0.132; WMD = -0.08 cm, 95% CI: -0.33, 0.17, P = 0.534; WMD = -0.05, 95% CI: -1.66, 1.55, P = 0.947, respectively). According to the results of the present systematic review and meta-analysis, there was no significant effect of pomegranate consumption on weight and body composition indices.

As an effective antimalarial drug, Dihydroartemisinin (DHA) is readily isolated from the traditional Chinese medicine of Artemisia annua. DHA is not only an autophagy promoter but also a substance with strong antitumor efficiency. The relationship between autophagy and inflammasomes has been suggested in hepatocellular carcinoma (HCC). However, there are few reports describing relationships between inflammasomes and autophagy in HCC therapy. The present study demonstrated that DHA suppressed cell proliferation in HepG2215 cells in a dose- and time-dependent manner. The inhibitory activity is mediated by autophagy, in which reactive oxygen species (ROS) production induced nuclear and mitochondrial DNA damage. Then, DHA were first shown to promote AIM2/caspase-1 inflammasome. Compared with the DHA group, the autophagy inhibitor 3-MA significantly inhibited the expressions of activated Caspase-1, a pyroptotic marker proteins. Meanwhile, repression of mTOR by rapamycin promoted autophagy and AIM2/caspase-1 activation. The caspase-1 inhibitor Z-YVAD-FMK also notably blocked autophagy cell death characterized by the downexpression of Beclin-1 and LC3-II. Additionally, the study demonstrated that DHA suppressed pseudopodium formation and cell mobility. Therefore, we first reveal a novel mechanism that DHA promotes AIM2/caspase-1 inflammasome, which contributes to autophagy in HepG2215 cells. Moreover, nuclear and mitochondrial DNA damage was also involved in this process via ROS production.

This study was aimed to quantify the antihyperglycemic effect of Nigella sativa (N. sativa). An in-depth search to identify clinical trials investigating the impact of N. sativa on glycemic indices via MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Library, and Google scholar databases were performed up to November 2018. We used a random effects model to estimate pooled effect size of fasting plasma glucose (FPG), postprandial blood glucose (PPBG), and hemoglobin A1c (HbA1c). A total of 17 randomized controlled trials investigating the effects of N. sativa on FPG, PPBG, and HbA1c were included. Meta-analysis suggested a significant association between N. sativa supplementation and reduction in FPG (weighted mean difference [WMD]: -9.93 mg/dl, 95% CI [-13.44, -6.41]), PPBG (WMD: -14.79 mg/dl, 95% CI [-24.19, -5.39]), and HbA1c (WMD: -0.57%, 95% CI [-0.77, -0.37]). Subgroup analysis revealed that N. sativa oil was more effective than N. sativa powder in reduction of FPG. To sum up, N. sativa consumption has a significant lowering effect on glycemic status. Further studies with prolonged durations and powerful design are needed to specify the exact mechanism, optimal dosage, and duration of N. sativa supplementation to obtain a beneficial effect on glycemic status.

Preclinical studies have shown beneficial effects of black seed (Nigella sativa L.) in the prevention and treatment of renal stones. Hence, we designed a study to evaluate the renal-stone-dissolving efficacy of black seed. Sixty patients with renal stones were randomly enrolled in two arms of a randomized, triple-blind, placebo-controlled, clinical trial. The patients were treated by black seed capsules (500 mg) or placebo two times per day for 10 weeks. Patients were assessed in terms of size of renal stones by using sonography before and after intervention. In the black seed group, 44.4% of patients excreted their stones completely, and the size of the stones remained unchanged and decreased in 3.7% and 51.8% of patients, respectively. In contrast, in the placebo group, 15.3% of the patients excreted their stones completely, 11.5% had reduction in stone size, 15.3% had increase in stone size, and 57.6% had no change in their stone size. The difference in the mean size of renal stones after the study was significant between the two groups (p < 0.05). N. sativa L., as compared with placebo, is demonstrated to have significant positive effects on disappearance or reduction of size of kidney stones.

Obesity is a metabolic disorder associated with adverse health consequences that has increased worldwide at an epidemic rate. This has encouraged many people to utilize nonprescription herbal supplements for weight loss without knowledge of their safety or efficacy. However, mounting evidence has shown that some herbal supplements used for weight loss are associated with adverse effects. Guarana seed powder is a popular nonprescription dietary herb supplement marketed for weight loss, but no study has demonstrated its efficacy or safety when administered alone. Wistar rats were fed four different diets (low-fat diet and Western diet with or without guarana supplementation) for 18 weeks. Metabolic parameters, gut microbiota changes, and toxicity were then characterized. Guarana seed powder supplementation prevented weight gain, insulin resistance, and adipokine dysregulation induced by Western diet compared with the control diet. Guarana induced brown adipose tissue expansion, mitochondrial biogenesis, uncoupling protein-1 overexpression, AMPK activation, and minor changes in gut microbiota. Molecular docking suggested a direct activation of AMPK by four guarana compounds tested here. We propose that brown adipose tissue activation is one of the action mechanisms involved in guarana supplementation-induced weight loss and that direct AMPK activation may underlie this mechanism. In summary, guarana is an attractive potential therapeutic agent to treat obesity.

Acute liver injury (ALI) is a life-threatening clinical syndrome. Long-lasting liver injury can lead to chronic hepatic inflammation and fibrogenic responses. Zerumbone (ZER), the main constituent of rhizomes of Zingiber zerumbet Smith, has a variety of functions including anticancer activity. We investigated the role of ZER on the progression of hepatotoxin-induced liver injury. Single or repeated injection of CCl4 was used to induce acute or chronic liver injury, respectively. Mice were orally administered with ZER (10, 50 mg/kg) during the experimental period. Histopathologic analysis and serum biochemical levels revealed that ZER had hepatoprotective activities against ALI. Similar effects of ZER on injured livers were confirmed by analyses of inflammation and apoptosis-related genes. Western blot analysis showed that protein levels of apoptotic molecules were decreased, whereas antiapoptotic protein levels were conversely increased in injured livers treated with ZER. Furthermore, chronic liver injury and its associated fibrogenesis in mice were reduced by ZER treatment. These findings from our in vivo experiments further indicate that ZER could alleviate hepatocellular toxicity and inhibit activation of primary hepatic stellate cells. Our results suggest that ZER might have potential as a safe and prophylactic alternative to prevent acute and chronic liver injury.