Betanin from Beetroot (Beta vulgaris L.) Regulates Lipid Metabolism and Promotes Fat Browning in 3T3-L1 Adipocytes.

Fat browning, which converts white adipose tissue to brown, has attracted attention as a promising strategy for the treatment of obesity. Betanin (BT) has been reported to have potential anti-obesity activity. 3T3-L1 cells were differentiated for 7 days during BT treatment. The BT concentration range for the study was determined using an MTT assay, and lipid accumulation was evaluated by Oil-Red-O staining. The expression of protein level was analyzed by Western blot. Immunofluorescence images were performed with confocal microscopy to visually show the amount and location of thermogenesis factor uncoupling protein1 (UCP1) and mitochondria. qRT-PCR was performed to evaluate mRNA expression. BT inhibited lipid accumulation and increased the expression of UCP1, peroxisome-proliferator-activated receptor gamma (PPARγ), and PPARγ coactivator-1 alpha (PGC-1α). In addition, the increases in beige adipocyte-specific markers were observed, supporting BT-mediated browning of the fat tissue. The UCP1 was localized in the inner membrane of the mitochondria, and its expression was associated with mitochondrial activation. Consistent with this, the mRNA expression of mitochondrial biogenesis markers increased in 3T3-L1 cells after BT treatment. Immunofluorescence staining also indicated an increased number of mitochondria and UCP1, respectively. Moreover, BT inhibited lipogenesis and enhanced lipolysis and fatty acid oxidation. This mechanism has been suggested to be mediated by an adenosine monophosphate-activated protein kinase (AMPK) pathway. BT induces fat browning and regulates lipid metabolism via the AMPK-mediated pathway in 3T3-L1 cells, suggesting that BT can be a promising candidate for controlling obesity.

Black Goji Berry (Lycium ruthenicum Murray): A Review of Its Pharmacological Activity.

Lycium ruthenicum Murray (LRM; commonly known as black goji berry or black wolfberry), a plant in the Solanaceae family, grows in the deserts of China's Qinghai-Tibet plateau. LRM is widely consumed in traditional Chinese medicine, and its fruits are frequently used as herbal remedies to treat heart disease, fatigue, inflammation, and other conditions. Many studies have reported that LRM is rich in functional phytochemicals, such as anthocyanins and polysaccharides, and has various pharmacological actions. This article reviews research on the biological and pharmacological effects of the constituents of LRM fruits. LRM has various pharmacological properties, such as antioxidant, anti-inflammatory, anti-radiation, immune-enhancing, anti-tumor, and protective effects. LRM has much promise as a dietary supplement for preventing many types of chronic metabolic disease.

Effect of Betanin, the Major Pigment of Red Beetroot (Beta vulgaris L.), on the Activity of Recombinant Human Cytochrome P450 Enzymes.

Most of the currently available drugs are derived from natural sources, but they are used only after extensive chemical modifications to improve their safety and efficacy. Natural products are used in health supplements and cosmetic preparations and have been used as auxiliary drugs or alternative medicines. When used in combination with conventional drugs, these herbal products are known to alter their pharmacokinetics and pharmacodynamics, reducing their therapeutic effects. Moreover, herb-drug interactions (HDIs) may have serious side effects, which is one of the major concerns in health practice. It is postulated that HDIs affect the pathways regulating cytochrome P450 enzymes (CYPs). Betanin, the chief pigment of red beetroot (Beta vulgaris L.), has various types of pharmacological activity, such as anti-inflammatory, antioxidant, and anticancer effects. However, the potential risk of HDIs for betanin has not yet been studied. Thus, we aimed to predict more specific HDIs by evaluating the effects of betanin on CYPs (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4), the major phase I metabolic enzymes, using fluorescence-/luminescence-based assays. Our results showed that betanin inhibited CYP3A4 activity in a dose-dependent manner (IC50 = 20.97 µΜ). Moreover, betanin acted as a competitive inhibitor of CYP3A4, as confirmed by evaluating Lineweaver-Burk plots (Ki value = 19.48 µΜ). However, no significant inhibitory effects were observed on other CYPs. Furthermore, betanin had no significant effect on CYP1A2, CYP2B6, or CYP2C9 induction in HepG2 cells. In conclusion, betanin acted as a competitive inhibitor of CYP3A4, and thus it should be used cautiously with other drugs that require metabolic enzymes as substrates. Additional in vivo studies and clinical trials are needed to further elucidate the HDIs of betanin.

In-package cold plasma treatment for microbial inactivation in plastic-pouch packaged steamed rice cakes.

In-package atmospheric cold plasma (ICP) treatment was investigated as a method to inactivate microorganisms in Korean steamed rice cakes (SRCs) packaged in plastic pouches. The effect against Escherichia coli O157:H7 increased with increasing ICP treatment power and time and using nylon-containing pouches. Moreover, E. coli O157:H7 growth was effectively inhibited at 4 and 25 °C when SRCs were in a pouch filled with an O2-CO2 (70 % and 30 %) gas. Under optimal treatment power (30 W), treatment time (4 min), and headspace-to-SRC volume ratio (7:1) conditions, ICP effectively inactivated E. coli O157:H7, Bacillus cereus spores, Penicillium chrysogenum, and indigenous aerobic bacteria, as well as yeast and molds in SRCs packaged with air in the nylon/low density polyethylene pouch by 2.2 ± 0.2 log CFU/g, 1.4 ± 0.2 log spores/g, 2.2 ± 0.3 log spores/g, 1.1 ± 0.2 log CFU/g, and 1.0 ± 0.1 log CFU/g, respectively. Furthermore, post-treatment storage was effective in preventing the growth of E. coli O157:H7 in SRCs at 4 °C and 25 °C when the pouch was filled with N2-CO2 (50 % and 50 %) or O2-CO2 (70 % and 30 %). Collectively, these findings indicate that ICP treatment effectively decontaminates SRCs and represents a potential non-thermal microbial decontamination technology for SRCs in pouch packaging.

Naringin promotes fat browning mediated by UCP1 activation via the AMPK signaling pathway in 3T3-L1 adipocytes.

Induction of the brown adipocyte-like phenotype in white adipocytes (fat browning) is considered a promising therapeutic strategy to treat obesity. Naringin, a citrus flavonoid, has antioxidant, anti-inflammatory, and anticancer activities. We examined the application of naringin as an anti-obesity compound based on an investigation of its induction of fat browning in 3T3-L1 adipocytes. Naringin did not induce lipid accumulation in differentiated 3T3-L1 adipocytes. Additionally, naringin reduced the expression levels of proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) involved in adipogenesis during lipid metabolism and increased the levels of PPARα and adiponectin involved in fatty acid oxidation. The expression levels of fat browning markers uncoupling protein 1 (UCP1; involved in thermogenesis) and PR domain containing 16 (PRDM16) increased. In addition, naringin treatment resulted in the activation of PPARγ coactivator 1-alpha (PGC-1α), a factor related to UCP1 transcription and mitochondrial biogenesis. Moreover, the expression of beige adipocyte-specific genes such as Cd137, Cited1, Tbx1, and Tmem26 was also induced. The small multi-lipid droplets characteristic of beige adipocytes indicated that naringin treatment increased the levels of all lipolysis markers (hormone-sensitive lipase [HSL], adipose triglyceride lipase [ATGL], perilipin [PLIN], and protein kinase A [PKA]). Adenosine monophosphate-activated protein kinase (AMPK) and UCP1 levels increased by treatment with naringin alone; this was possibly mediated by the stimulation of the AMPK signaling pathway. According to mechanistic studies, naringin activated the thermogenic protein UCP1 via the AMPK signaling pathway. In conclusion, naringin induces fat browning and is a promising therapeutic agent for metabolic disorders based on the regulation of lipid metabolism.

Pharmacological Activity of Garcinia indica (Kokum): An Updated Review.

Garcinia indica (commonly known as kokum), belonging to the Clusiaceae family (mangosteen family), is a tropical evergreen tree distributed in certain regions of India. It has been used in culinary and industrial applications for a variety of purposes, including acidulant in curries, pickles, health drinks, wine, and butter. In particular, G. indica has been used in traditional medicine to treat inflammation, dermatitis, and diarrhea, and to promote digestion. According to several studies, various phytochemicals such as garcinol, hydroxycitric acid (HCA), cyanidin-3-sambubioside, and cyanidin-3-glucoside were isolated from G. indica, and their pharmacological activities were published. This review highlights recent updates on the various pharmacological activities of G. indica. These studies reported that G. indica has antioxidant, anti-obesity, anti-arthritic, anti-inflammatory, antibacterial, hepatoprotective, cardioprotective, antidepressant and anxiolytic effects both in vitro and in vivo. These findings, together with previously published reports of pharmacological activity of various components isolated from G. indica, suggest its potential as a promising therapeutic agent to prevent various diseases.

Saikosaponin A and D Inhibit Adipogenesis via the AMPK and MAPK Signaling Pathways in 3T3-L1 Adipocytes.

Obesity is a lipid metabolism disorder caused by genetic, medicinal, nutritional, and other environmental factors. It is characterized by a complex condition of excess lipid accumulation in adipocytes. Adipogenesis is a differentiation process that converts preadipocytes into mature adipocytes and contributes to excessive fat deposition. Saikosaponin A (SSA) and saikosaponin D (SSD) are triterpenoid saponins separated from the root of the Bupleurum chinensis, which has long been used to treat inflammation, fever, and liver diseases. However, the effects of these constituents on lipid accumulation and obesity are poorly understood. We investigated the anti-obesity effects of SSA and SSD in mouse 3T3-L1 adipocytes. The MTT assay was performed to measure cell viability, and Oil Red O staining was conducted to determine lipid accumulation. Various adipogenic transcription factors were evaluated at the protein and mRNA levels by Western blot assay and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Here, we showed that SSA and SSD significantly inhibited lipid accumulation without affecting cell viability within the range of the tested concentrations (0.938-15 µM). SSA and SSD also dose-dependently suppressed the expression of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein alpha (C/EBPα), sterol regulatory element binding protein-1c (SREBP-1c), and adiponectin. Furthermore, the decrease of these transcriptional factors resulted in the repressed expression of several lipogenic genes including fatty acid binding protein (FABP4), fatty acid synthase (FAS), and lipoprotein lipase (LPL). In addition, SSA and SSD enhanced the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase (ACC), and inhibited the phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2) and p38, but not c-Jun-N-terminal kinase (JNK). These results suggest that SSA and SSD inhibit adipogenesis through the AMPK or mitogen-activated protein kinase (MAPK) pathways in the early stages of adipocyte differentiation. This is the first study on the anti-adipogenic effects of SSA and SSD, and further research in animals and humans is necessary to confirm the potential of saikosaponins as therapeutic agents for obesity.

Antidiabetic Flavonoids from Fruits of Morus alba Promoting Insulin-Stimulated Glucose Uptake via Akt and AMP-Activated Protein Kinase Activation in 3T3-L1 Adipocytes.

Morus alba (Moraceae), known as white mulberry, has been used to treat fever, protect against liver damage, improve eyesight, and lower blood sugar levels in traditional oriental medicine. Few studies have been conducted on the antidiabetic compounds identified from M. alba and their underlying mechanisms of action. Consequently, in this study, the fruits of M. alba were investigated for potential antidiabetic natural products using 3T3-L1 adipocytes. Phytochemical analysis of the ethanolic extract of M. alba fruits, followed by high-performance liquid chromatography (HPLC), purification led to the isolation of two main compounds: rutin and quercetin-3-O-ß-d-glucoside (Q3G). Long-term use of available drugs for treating type 2 diabetes ((T2D) is often accompanied by undesirable side effects, which have generated increased interest in the development of more effective and safer antidiabetic agents. Examination of the isolated compounds, rutin and Q3G, for antidiabetic or anti-obesity properties or both in 3T3-L1 adipocytes demonstrated that they both improved glucose uptake via Akt-mediated insulin signaling pathway or AMP-activated protein kinase (AMPK) activation in 3T3-L1 adipocytes. The compounds also showed a positive effect on lipid accumulation in adipocytes, suggesting that glucose uptake occurred through activation of the Akt and AMPK signaling pathway without inducing adipogenesis. Taken together, our findings suggest that rutin and Q3G in M. alba fruits have the potential to induce fewer side effects such as weight gain, and these active compounds could be potential therapeutic candidates for the management of T2D.