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.

Anti-influenza A Virus Effects and Mechanisms of Emodin and Its Analogs via Regulating PPARα/γ-AMPK-SIRT1 Pathway and Fatty Acid Metabolism.

The peroxisome proliferator-activated receptor (PPAR) α/γ-adenosine 5'-monophosphate- (AMP-) activated protein kinase- (AMPK-) sirtuin-1 (SIRT1) pathway and fatty acid metabolism are reported to be involved in influenza A virus (IAV) replication and IAV-pneumonia. Through a cell-based peroxisome proliferator responsive element- (PPRE-) driven luciferase bioassay, we have investigated 145 examples of traditional Chinese medicines (TCMs). Several TCMs, such as Polygonum cuspidatum, Rheum officinale Baillon, and Aloe vera var. Chinensis (Haw.) Berg., were found to possess high activity. We have further detected the anti-IAV activities of emodin (EMO) and its analogs, a group of common important compounds of these TCMs. The results showed that emodin and its several analogs possess excellent anti-IAV activities. The pharmacological tests showed that emodin significantly activated PPARα/γ and AMPK, decreased fatty acid biosynthesis, and increased intracellular ATP levels. Pharmaceutical inhibitors, siRNAs for PPARα/γ and AMPKα1, and exogenous palmitate impaired the inhibition of emodin. The in vivo test also showed that emodin significantly protected mice from IAV infection and pneumonia. Pharmacological inhibitors for PPARα/γ and AMPK signal and exogenous palmitate could partially counteract the effects of emodin in vivo. In conclusion, emodin and its analogs are a group of promising anti-IAV drug precursors, and the pharmacological mechanism of emodin is linked to its ability to regulate the PPARα/γ-AMPK pathway and fatty acid metabolism.

Therapeutic Promises of Chlorogenic Acid with Special Emphasis on its Anti-Obesity Property.

BACKGROUND: Chlorogenic acid (CGA) is a quinic acid conjugate of caffeic acid. It is an ester formed between caffeic acid and the 3-hydroxyl of L-quinic acid. This polyphenol is naturally present in substantial amount in the green coffee beans. Minor quantities of CGA are also reported in apples, eggplant, blueberries, tomatoes, strawberries and potatoes. CGA is reported to be beneficial in hypertension, hyperglycemia, antimicrobial, antitumor, memory enhancer, weight management etc. Further, it is also reported to have anticancer, antioxidant and anti-inflammatory activities. Since the last decade, CGA drew public attention for its widely recommended use as a medicine or natural food additive supplement for the management of obesity. OBJECTIVE: The current review explores the medicinal promises of CGA and emphasizes on its antiobese property as reported by various scientific reports and publication. CONCLUSION: CGA shows promises as an antioxidant, glycemic control agent, anti-hypertensive, antiinflammatory, antimicrobial, neuro-protective and anti-obesity agent. It primarily activates the AMPactivated protein kinase, inhibits 3-hydroxy 3-methylglutaryl coenzyme-A reductase and strengthens the activity of carnitine palmitoyltransferase to control the obesity.

Effect of free and nano-encapsulated curcumin on treatment and energetic metabolism of gerbils infected by Listeria monocytogenes.

Bacterial infections require special care since the indiscriminate use of antibiotics to treat them has been linked to the emergence of resistant strains. In this sense, phytoterapeutic alternatives such as curcumin and its nanocapsules have emerged as a promising supplement in optimizing availability of bioactives and reducing the development of antimicrobial resistance. Thus, the aim of this study was to verify the effects of pure and nanoencapsulated curcumin in the treatment of experimental listeriosis in gerbils regarding many aspects including antibacterial effect, antioxidant mechanisms involved and the energetic metabolism. Four groups were used containing 6 animals each: T0 (control), T1 (infected), T2 (infected and treated with free curcumin - dose of 30 mg/kg/day) and T3 (infected and treated with nanocapsules containing curcumin - a dose of 3 mg/kg/day). Treated animals received curcumin for 6 consecutive days starting 24 h after Listeria monocytogenes infection. All animals were euthanized on the 12th day after L. monocytogenes infection. Quantitative polymerase chain reaction (qPCR) identified L. monocytogenes DNA in the spleens of all animals of the T1 group, as well as T2 (2 out of 6) and T3 (5 out of 6). The weight of the spleens confirmed the infection, since it was larger in the T1 group, differing statistically from T0, and similarly to T2 and T3. Hepatic histopathological examination showed mild infiltration of neutrophils and macrophages, except for the T3 group (only 1/6). In the liver, the pyruvate kinase activity was higher in T1 and T2 compared to T0 and T3. The adenylate kinase activity did not differ between groups. The Na+/K+ATPase activity was lower in T1 group compared to T0 and T3. Lipoperoxidation was lower in the T3 group compared to groups T0, T1 and T2. The antioxidant capacity against peroxyl radicals was higher in T1, T2 and T3 groups compared to T0. In conclusion, free curcumin showed potent antibacterial effects; however, the nanoencapsulated form was able to minimize the effects caused by L. monocytogenes regarding tissue injury, changes on enzymes of the energetic metabolism, in addition to an antioxidant effect against lipoperoxidation.

Terminalia bellirica (Gaertn.) Roxb. Extract and Gallic Acid Attenuate LPS-Induced Inflammation and Oxidative Stress via MAPK/NF-κB and Akt/AMPK/Nrf2 Pathways.

Excessive oxidative stress plays a critical role in the progression of various diseases. Recently, we showed that Terminalia bellirica (Gaertn.) Roxb. extract (TBE) inhibits inflammatory response and reactive oxygen species (ROS) production in THP-1 macrophages. However, molecular mechanisms underlying anti-inflammatory and antioxidant activities of TBE and its major polyphenolic compounds gallic acid (GA) and ellagic acid (EA) remain unclear. We found that TBE and GA attenuated LPS-induced inflammatory mediator expression, ROS production, and activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) in RAW 264 macrophages. Furthermore, TBE and GA increased antioxidant enzyme expression along with upstream mediators nuclear factor erythroid-2-related factor 2 (Nrf2), Akt, and AMP-activated protein kinase (AMPK). Importantly, knockdown of Nrf2 by siRNA and specific inhibition of Akt and AMPK significantly reduced antioxidant enzyme expression induced by TBE and GA. Finally, in vivo effects on histopathology and gene expression were assessed in tissues collected after intraperitoneal injection of LPS with or without TBE treatment. TBE enhanced antioxidant enzyme expression and improved acute kidney injury in LPS-shock model mice. In conclusion, TBE and GA exert protective effects against inflammation and oxidative stress by suppressing MAPK/NF-κB pathway and by activating Akt/AMPK/Nrf2 pathway. These results suggest that TBE and GA might be effective for the treatment of inflammation-related diseases.

Ethanol extracts of Aster yomena (Kitam.) Honda inhibit adipogenesis through the activation of the AMPK signaling pathway in 3T3-L1 preadipocytes.

The leaves of Aster yomena (Kitam.) Honda have long been used as a traditional herb for treating disorders including coughs, asthma, and insect bites. According to recent studies, A. yomena leaf extracts have several pharmacological properties, including anti-inflammatory, antioxidant, and anti-asthmatic activities. However, little information is available regarding their anti-obesity effect. In this study, we investigated the inhibitory effect of the ethanol extracts of A. yomena leaves (EEAY) on adipocyte differentiation and adipogenesis using 3T3-L1 preadipocytes. When 3T3-L1 preadipocytes were treated with various concentrations of EEAY (ranging from non-toxic), the number of lipid droplets, lipid content, and triglyceride production, the typical characteristics of adipocytes, were suppressed in a concentration-dependent manner. During this process, EEAY significantly reduced the expression of adipogenic transcription factors, including peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein α and ß, and sterol regulatory element-binding protein-1c. In addition, EEAY was also found to potently inhibit the expression of adipocyte-specific genes, including adipocyte fatty acid-binding protein and leptin. In particular, EEAY treatment effectively enhanced the activation of the AMP-activated protein kinase (AMPK) signaling pathway; however, the co-treatment with compound C, an inhibitor of AMPK, significantly restored the EEAY-induced inhibition of pro-adipogenic transcription factors and adipocyte-specific genes. These results indicate that EEAY may exert an anti-obesity effect by controlling the AMPK signaling pathway, suggesting that the leaf extract of A. yomena may be a potential anti-obesity agent.