BACKGROUND: Hodgsonia heteroclita has been known as an important traditionally consumed medicinal plant of North-East India known to have antidiabetic properties. This study aims to investigate the effects of the ethanolic fruit extract of Hodgsonia heteroclita against hyperglycemia and hyperlipidemia by using streptozotocin (STZ) treated diabetic mice.
METHODS: The fruits of H. heteroclita were collected from the various parts of Kokrajhar district, Assam India (Geographic coordinates: 26°24\'3.85″ N 90°16\'22.30″ E). Basic morphological evaluations were carried out by the Botanical Survey of India, Eastern circle, Shillong, who also certified and identified the plant. Hexane, chloroform, and ethanolic extracts of the fruit of H. heteroclita were investigated for α-amylase inhibition assay as a rapid screening tool for examining anti-diabetic activity. The efficacy of ethanolic extract at a dose of 100, 200, and 300 mg/kg body weight was tested for 21 days in STZ-induced diabetic mice. The body weight, fasting plasma glucose and serum lipids, and hepatic glycogen levels were measured in experimental animals to examine the antihyperglycemic and antihyperlipidemic efficacy of the extract. Both HPTLC and LC-MS analysis was performed to examine the phyotochemicals present in the ethanolic extract of H. heteroclita.
RESULTS: It has been observed that treatment with the ethanolic extract dose-dependently reduced the plasma glucose levels, total cholesterol, low density lipoprotein-cholesterol, very low-density lipoprotein-cholesterol, triglyceride, and increased the body weight, liver glycogens and high-density lipoprotein-cholesterol in STZ treated diabetic mice. HPTLC demonstrated the presence of triterpene compounds and LC-MS analysis revealed the presence Cucurbitacin I, Cucurbitacin E, and Kuguacin G as the triterpene phytoconstituents.
CONCLUSIONS: The present study demonstrated that ethanolic fruit extract of H. heteroclita improved both glycemic and lipid parameters in mice model of diabetes.

UNASSIGNED: The epidemic of nonalcoholic fatty liver disease (NAFLD) and its metabolic effects present a serious public health concern. We hypothesized that the Ramadan fasting model (RFM), which involves fasting from dawn to dusk for a month, could provide potential therapeutic benefits and mitigate NAFLD. Accordingly, we aimed to validate this hypothesis using obese male rats.
UNASSIGNED: Rats were split into two groups (n = 24 per group), and they were given either a standard (S) or high-fat diet (HFD) for 12 weeks. During the last four weeks of the study period, both S- and HFD-fed rats were subdivided into eight groups to assess the effect of RFM with/without training (T) or glucose administration (G) on the lipid profile, liver enzymes, and liver structure (n = 6/group).
UNASSIGNED: The HFD+RFM group exhibited a significantly lower final body weight than that in the HFDC group. Serum cholesterol, low-density lipoprotein, and triglyceride levels were significantly lower in the HFD+RFM, HFD+RFM+T, and HFD+RFM+G groups than those in the HFDC group. Compared with the HFDC group, all groups had improved serum high-density lipoprotein levels. Furthermore, HFD groups subjected to RFM had reduced serum levels of aspartate transaminase and alanine transaminase compared with those of the HFD-fed group. Moreover, the liver histology improved in rats subjected to RFM compared with that of HFD-fed rats, which exhibited macro- and micro-fat droplet accumulation.
UNASSIGNED: RFM can induce positive metabolic changes and improve alterations associated with NAFLD, including weight gain, lipid profile, liver enzymes, and hepatic steatosis.

Lovastatin (Lov) is a lipid-lowering agent, with 5% bioavailability (BA) due to extensive first pass metabolism and poor solubility. To enhance dissolution and in vivo effects, Lov solid self microemulsifying drug delivery system (SMEDDS) and liquisolid systems were developed and evaluated to select superior one. Solubilities were determined in oils, surfactants, and cosurfactants. Ternary phase diagrams were constructed and selected the one which showed maximum emulsion zone. In vitro dissolution, DSC, SEM and PXRD studies were used to characterize the developed formulations. In vivo studies were conducted on optimal formulations in wistar rats. Based on solubilities, Capmul PG8 and Capmul MCM were preferred as oils, Labrasol and Transcutol P as surfactant and cosurfactant. Here, Syloid XDP carrier showed better adsorption capacity among others, hence was used in optimal solid SMEDDS (SX) and liquisolid (LS) formulations. Dissolution study results showed significant improvement in release when compared to pure drug. DSC, SEM, and PXRD results indicated the loss of drug crystallinity in optimal formulations. In pharmacokinetic (PK) study, SX and LS showed 2.57 and 1.43 fold improvements in AUC, when compared to that of coarse suspension (CS). In pharmacodynamic (PD) study, hyperlipidemia was induced by Triton X-100. CS and LS treatments showed a decline in hyperlipidemic levels at 4 h. But, SX-treated group showed early onset of decline at 2 h. Further, the duration of anti-hyperlipidemia was at least 12 h extra when compared to CS and LS. This study confirmed the superiority of SX over LS in PK and PD effects.

Simvastatin is an established anti-hyperlipidemic drug and few studies have indicated its role in the mitigation of oxidative stress. However, a systematic study considering molecular binding/interaction of simvastatin with anti-oxidant enzymes followed by confirmational in vitro and in vivo studies have never been done. We investigated the molecular binding of simvastatin with multiple anti-oxidant enzymes and assessed their levels after the treatment of simvastatin in vitro and in vivo. This study is the first to show the molecular binding of simvastatin to catalase through molecular docking analysis. Moreover, the anti-oxidative properties of simvastatin have not been studied in Lipopolysaccharide (LPS) induced oxidative stress in HepG2 cells. We found that simvastatin effectively attenuated oxidative stress in LPS induced HepG2 cells and high-fat diet (HFD) fed hyperlipidemic rats by increasing the levels of antioxidant enzymes. The activity of catalase and superoxide dismutase (SOD) both increased significantly in oxidatively stressed HepG2 cells after the treatment with simvastatin (10 ​μM, 24 ​h). In addition to this, he original cell morphology of oxidatively stressed cells was restored by simvastatin, and an increase in antioxidant enzymes, catalase (0.08 U/cells to 0.12 U/cells), and SOD (0.57 U/cells to 0.74 U/cells) was also noted in HepG2 cells. Furthermore, a significant increase in the antioxidant enzymes such as Catalase, SOD, and reduced glutathione (GSH) was noted after simvastatin treatment in the HFD model. Moreover, we also observed degradation of by-products of lipid peroxidation thiobarbituric acid reactive substances (TBARs), nitric oxide (NO), and protein carbonyl levels. This indicates that simvastatin enhances anti-oxidant enzyme activities and can be repurposed for the treatment of oxidative stress in liver diseases in humans after extensive clinical trials.

Berberine (BBR) is a plant-origin quaternary isoquinoline alkaloid presenting exogenous cholesterol lowering and anti-hyperlipidemia therapeutic effects. The aim of this study was to design and generate BBR-loaded proliposomes (PLs) as solid templates for high-dose liposomes and consequently, to enhance the oral bioavailability and therapeutic effect of BBR. An air-suspension coating (layering) method was used for generating BBR-loaded PLs. The size, distribution size, morphology, and entrapment efficiency (EE) of the final reconstituted liposomes were assessed. The oral bioavailability and endogenous cholesterol lowering effects of BBR loaded in liposomes were investigated in rats and mice, respectively. The BBR-loaded PLs showed a smooth BBR-embedded film around micron-scale carrier particles (mannitol). The reconstituted BBR-loaded liposomes had a nano-scale average size (116.6 ± 5.8 nm), narrow size distribution (polydispersity index, PDI 0.269 ± 0.038), and high EE (87.8 ± 1.0%). The oral bioavailability of reconstituted BBR-loaded liposomes at a dose of 100 mg/kg in rats was increased even 628% compared to that obtained with pure BBR (according to 90% confidence interval). The BBR-loaded liposomes at the daily oral dose 100 mg/kg in P-407- reduced total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C) in hyperlipidemic mice by 15.8%, 38.2%, and 57.0%, respectively.

Stevia rebaudiana Bertoni is a native plant to Paraguay. The extracts have been used as a famous sweetening agent, and the bioactive components derived from stevia possess a broad spectrum of therapeutical potential for various illnesses. Among its medicinal benefits are anti-hypertensive, anti-tumorigenic, anti-diabetic, and anti-hyperlipidemia. Statins (3-hydro-3-methylglutaryl-coenzyme A reductase inhibitor) are a class of drugs used to treat atherosclerosis. Statins are explicitly targeting the HMG-CoA reductase, an enzyme in the rate-limiting step of cholesterol biosynthesis. Despite being widely used in regulating plasma cholesterol levels, the adverse effects of the drug are a significant concern among clinicians and patients. Hence, steviol glycosides derived from stevia have been proposed as an alternative in replacing statins. Diterpene glycosides from stevia, such as stevioside and rebaudioside A have been evaluated for their efficacy in alleviating cholesterol levels. These glycosides are a potential candidate in treating and preventing atherosclerosis provoked by circulating lipid retention in the sub-endothelial lining of the artery. The present review is an effort to integrate the pathogenesis of atherosclerosis, involvement of lipid droplets biogenesis and its associated proteins in atherogenesis, current approaches to treat atherosclerosis, and pharmacological potential of stevia in treating the disease.

Allium cepa is used for the prevention and treatment of hyperlipidemia-related diseases such as atherosclerosis in the folk. This study was mainly aimed at investigating the effects of A. cepa extract (ACE) enriched in polyphenols on hyperlipidemia Sprague-Dawley (SD) experiment rat models. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA), and superoxide dismutase (SOD) activity in serum and liver were measured using ELISA kits. In addition, hematoxylin-eosin (HE) technique was used to observe the liver and the aortic arch pathology. Moreover, western blotting (WB) method was applied to analyze LDL receptor (LDLR) and 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase (HMGCR) in liver. As a result, quercetin (2.42 mg/g DW) and isoquercitrin (4.60 mg/g DW) were the main constituents of ACE using HPLC analysis. Furthermore, ACE reduced the levels of TC, TG, LDL-C, and MDA, and increased HDL levels and elevated SOD activity both in serum and liver in hyperlipidemic SD rats (p < .05). HE results showed that liver fat drops of the rats in ACE group were obviously decreased, and the lipid and foam cells of the aortic arch of the rats in ACE group were markedly ameliorated. WB results showed that ACE promoted the degradation of HMGCR and increased LDLR expression in liver (p < .05). In conclusion, ACE alleviated hyperlipidemia with downregulation of HMGCR and upregulation of LDLR. PRACTICAL APPLICATIONS: Atherosclerosis, a major cardiovascular disease, is the leading cause of mortality and morbidity in the developed countries. Moreover, accumulating data indicate that, during atherosclerosis development, hyperlipidemia is an important risk factor. To date, hyperlipidemia is mainly treated with hyperlipidemic agents including statins, in spite of the side effects and poor tolerance in some patients. In addition, Allium cepa is a medicinal and edible plant. Furthermore, A. cepa is used for the prevention and treatment of hyperlipidemia-related diseases such as atherosclerosis in the folk. But the underlying mechanism is still unclear. In fact, this research showed that A. cepa extract (ACE) alleviated hyperlipidemia with downregulation of HMGCR and upregulation of LDLR, suggesting that ACE might be a potential option for hyperlipidemia as non-statin lipid-lowering agent.

Cordyceps is a rare naturally occurring entomopathogenic fungus usually found at high altitudes on the Himalayan plateau and a well-known medicinal mushroom in traditional Chinese medicine. Cordyceps contains various bioactive components, out of which, cordycepin is considered most vital, due to its utmost therapeutic as well as nutraceutical potential. Moreover, the structure similarity of cordycepin with adenosine makes it an important bioactive component, with difference of only hydroxyl group, lacking in the 3\' position of its ribose moiety. Cordycepin is known for various nutraceutical and therapeutic potential, such as anti-diabetic, anti-hyperlipidemia, anti-fungal, anti-inflammatory, immunomodulatory, antioxidant, anti-aging, anticancer, antiviral, hepato-protective, hypo-sexuality, cardiovascular diseases, antimalarial, anti-osteoporotic, anti-arthritic, cosmeceutical etc. which makes it a most valuable medicinal mushroom for helping in maintaining good health. In this review, effort has been made to bring altogether the possible wide range of cordycepin\'s nutraceutical potential along with its pharmacological actions and possible mechanism. Additionally, it also summarizes the details of cordycepin based nutraceuticals predominantly available in the market with expected global value. Moreover, this review will attract the attention of food scientists, nutritionists, pharmaceutical and food industries to improve the use of bioactive molecule cordycepin for nutraceutical purposes with commercialization to aid and promote healthy lifestyle, wellness and wellbeing.

BACKGROUND: The Si-miao-yong-an decoction (SMYAD) is a famous traditional Chinese medicinal formula that has been used for centuries in ancient China for treating thromboangiitis obliterans. Because of its long history of use, it has been used to treat patients in China for thousands of years. In recent years, SMYAD has been widely used for treating cardiovascular and endocrine diseases. It was shown to significantly increase high-density lipoprotein-cholesterol levels and reduce total cholesterol and low-density lipoprotein-cholesterol levels in the serum.
OBJECTIVE: Herein, a serum metabonomics approach based on the HPLC-MS/MS method was adopted to evaluate the therapeutic effect of SMYAD on high-fat diet-induced hyperlipidemia, and investigate the mechanisms for treating hyperlipidemia.
METHODS: Firstly, the change in body weight, liver histopathology, and serum biochemistry, including that in the levels of hepatotoxicity-related enzymes, oxidative stress indexes, and inflammatory factors were monitored in rats, to evaluate the therapeutic effect of SMYAD on high-fat diet-induced hyperlipidemia. Then, a serum metabolomics approach was applied, to cluster different groups using principle component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), as well as to screen out sensitive and reliable biomarkers. Finally, the metabolic pathways associated with specific biomarkers were analyzed, to understand the possible mechanism underlying the action of SMYAD.
RESULTS: The results indicated that SMYAD had significant anti-hyperlipidemic, anti-oxidant, and anti-inflammatory effects. Based on the results of serum metabolomics analysis, the hyperlipidemic rats showed completely different results compared to the control rats; metabolite profiles of rats from the SMYAD treatment groups showed a trend comparable to those of the normal control group in a dose-dependent manner. Besides, twelve biomarkers associated with pyruvate metabolism, taurine and hypotaurine metabolism, TCA cycle, bile acid metabolism, and glucose metabolism were identified and confirmed, to clarify the mechanism of action of SMYAD.
CONCLUSIONS: Using metabonomics technology, it was predicted that the therapeutic effects of SMYAD were associated with its anti-oxidation as well as anti-inflammatory activities and the adjustment of the pyruvate, taurine as well as hypotaurine metabolism pathways in the hyperlipidemic state. This study provided evidence regarding the clinical application of SMYAD and thoroughly explored the mechanism underlying the action of this traditional Chinese medicine.

Background and Objectives: Dyslipidemia is gaining much attention among healthcare professionals because of its high association with the malfunctioning of a number of normal physiological and metabolic processes in the body. Obesity is directly interconnected with dyslipidemia and is said to be a denouement of hyperlipidemia and, if left untreated, may lead to intense damage to organs that are directly involved in fat metabolism. The objective of this study was to investigate the synergistic antiobesity and anti-hyperlipidemic activities along with hepato- and renoprotective potential of nanoemulsomes (NES) of lovastatin (LTN)-loaded ginger (GR) and garlic (GL) oils. Materials and Methods: LTN nanoemulsomes co-encapsulated with GR oil and GL oil were prepared by a thin hydration technique. Eight-week-old male Wistar rats weighing 200-250 g were induced with hyperlipidemia via a high-fat diet (HFD) comprising 40% beef tallow. Body weight, serum biochemical lipid parameters, and those for liver and kidney functions, serum TC, LDL-C, vLDL-C, HDL-C, TG, atherogenic index (AI), ALT, AFT, ALP, γ-GT, total protein (TP), serum albumin and globulin ratio (A/G), serum creatinine, blood urea nitrogen (BUN) and blood urea, and histopathology of hematoxylin and eosin (H&E) stained liver and kidney sections of all aforementioned groups were examined in the treated animals. Results: Nanoemulsomes of LTN-loaded GR and GL oils provided synergistic effects with LTN, exerted better ameliorative actions in reducing serum TC, LDL-C, vLDL-C, triglycerides, and AI, and improved serum HDL-C levels. Serum ALT, AST, ALP, and γ-GT levels were in the normal range for nanoemulsome groups. H&E stained liver and kidney sections of these animals confirmed better hepatoprotective and renoprotective effects than LTN alone. Serum biochemical parameters for renal functions also claimed to be in the moderate range for nanoemulsome-treated groups. Conclusion: This study demonstrated that nanoemulsomes of LTN-loaded GR and GL oils synergistically provided better antihyperlipidemic, hepatoprotective, and renoprotective effects as compared to LTN alone.