stevioside and Inflammation

Osteoarthritis (OA) is a joint disease that is characterized by articular cartilage degeneration and destruction. Stevioside (SVS) is a diterpenoid glycoside extracted from Stevia rebaudiana Bertoni with some specific effects against inflammatory and apoptotic, whereas it is still unclear what function SVS has in osteoarthritis. This study focuses on the anti-inflammatory and anti-apoptosis functions of SVS on chondrocytes induced by interleukin (IL)-1beta, and the role of SVS in an osteoarthritis model for mice. We can detect the production of inflammatory factors such as nitric oxide (NO) and prostaglandin E2 (PGE2) using real-time quantitative polymerase chain reaction (RT-qPCR), the Griess reaction, and enzyme linked immunosorbent assay (ELISA). On the basis of Western blot, we have observed the protein expressions of cartilage matrix metabolism, inflammatory factors, and apoptosis of chondrocytes. Simultaneously, the pharmacological effects of SVS in mice were evaluated by hematoxylin and eosin (HE), toluidine blue, Safranin O, and immunohistochemical staining. The results show that SVS slows extracellular matrix degradation and chondrocyte apoptosis. In addition, SVS mediates its cellular effect by inhibiting the activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling pathways. Meanwhile, molecular docking studies revealed that SVS has excellent binding capabilities to p65, extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). The study suggests that SVS can be developed as a potential osteoarthritis treatment.

Topics: Animals; Cartilage, Articular; Chondrocytes; Extracellular Signal-Regulated MAP Kinases; Inflammation; Interleukin-1beta; Mice; Molecular Docking Simulation; NF-kappa B; Osteoarthritis

Osteoarthritis (OA) is a common, progressive, and chronic disorder of the joints that is characterized by the inflammation and degradation of articular cartilage and is known to significantly impair quality of daily life. Stevioside (SVS) is a natural diterpenoid glycoside that has anti-inflammatory benefits. Hence, in the current research, it was hypothesized that SVS might exert anti-inflammatory effects on articular chondrocytes and alleviate cartilage degradation in mice with OA. The expression of inflammatory cytokines, like inducible nitric oxide synthase (iNOS), NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), and cyclooxygenase-2 (COX-2) in chondrocytes after interleukin-1β (IL-1β) exposure, was inhibited by the pretreatment of SVS. As well, SVS inhibited the reduction of collagen II and sry-box transcription factor 9 (SOX9) in chondrocytes stimulated by IL-1β and suppressed the expression of MMP3 and MMP13. Further, after treatment with SVS, cell cytometry, autophagy flux, and related protein expression showed diminished cell apoptosis and reduced autophagy impairment. Moreover, SVS blocked the activation of phosphoinositide-3-kinase/Akt/nuclear factor-kappa beta (PI3K/Akt/NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways stimulated by IL-1β. This resulted in decreased cellular inflammation. In vivo experiments with intra-articular injections of SVS in mice with the DMM mouse model demonstrated a decrease in cartilage degradation and an improvement in subchondral bone remodeling. After the integrin αVβ3-related knockdown using siRNA, a reversed effect was observed on the anti-inflammatory, anabolic promoting, catabolic blocking, and NF-κB and MAPK signaling pathway inhibition of SVS on chondrocytes treated with IL-1β. The above findings highlighted that SVS blocked IL-1β, triggered an inflammatory response in mice chondrocytes, and prevented cartilage degradation in vivo through integrin αVβ3. This suggested that SVS might serve as a novel therapeutic option for OA.

Topics: Animals; Anti-Inflammatory Agents; Cartilage, Articular; Cells, Cultured; Chondrocytes; Inflammation; Integrin alphaVbeta3; Interleukin-1beta; Mice; NF-kappa B; Osteoarthritis; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt

Excessive sugar intake has become a major challenge in modern societies. Stevioside is a promising non-calorie sweetener with anti-inflammatory effects; however, its effects on the oral environment and periodontitis remain unclear. Therefore, this study explores the effect of stevioside on periodontitis in mice.. Mice were divided into four groups, namely, control, treated with water, and periodontitis models, established using 5 - 0 silk sutures ligation around the second molar then infected the oral cavity with Porphyromonas gingivalis (P. gingivalis) viscous suspension, divided into three groups treated with 0.1% stevioside (P + S), 10% glucose (P + G), or water (P). Micro-CT scanning was used to assess alveolar bone resorption, while RT-PCR was used to evaluate the inflammatory factors expression and P. gingivalis invasion in the gingiva. The composition of the oral bacteria was analysed using 16 S rRNA sequence in the saliva. In addition, P. gingivalis was co-cultured with stevioside at different concentrations in vitro, and bacterial activity was detected via optical density values and live/dead staining. The virulence was detected using RT-PCR, while biofilm formation was detected using scanning electron microscopy.. Compared with 10% glucose, treatment with 0.1% stevioside reduced alveolar bone absorption and osteoclasts while decreasing IL-6, TNF-α, IL-1β, and P. gingivalis in the gingiva of periodontitis mice. The CEJ-ABC distance in the P + S group was significantly lower than that in the P and P + G groups (P < 0.05). Moreover, the composition of the oral bacteria in the P + S group was similar to that of the control. In vitro stevioside treatment also reduced the bacterial activity and toxicity of P. gingivalis in a dose-dependent manner and affected its biofilm composition.. Our results indicate that, compared with 10% glucose, 0.1% stevioside intake can reduce alveolar bone resorption and inflammation in periodontal tissues in mice; the bacterial composition following 0.1% stevioside intake was similar to that of a healthy environment. In vitro, high concentrations of stevioside reduced P. gingivalis activity, biofilm formation, and virulence expression. Therefore, stevioside is a potential alternative to glucose for patients with periodontitis.

Topics: Alveolar Bone Loss; Animals; Bacteria; Disease Models, Animal; Glucose; Humans; Inflammation; Mice; Periodontitis; Porphyromonas gingivalis; Water

Obesity is a public health problem characterized by increased body weight due to abnormal adipose tissue expansion. Bioactive compound consumption from the diet or intake of dietary supplements is one of the possible ways to control obesity. Natural products with adipogenesis-regulating potential act as obesity treatments. We evaluated the synergistic antiangiogenesis, antiadipogenic and antilipogenic efficacy of standardized rebaudioside A, sativoside, and theasaponin E1 formulations (RASE1)

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Angiogenesis Inhibitors; Animals; Biological Products; Disease Models, Animal; Diterpenes, Kaurane; Drug Compounding; Drug Synergism; Female; Glucosides; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Lipid Metabolism; Lipogenesis; Lipolysis; Mice; Mice, Inbred ICR; Obesity; Oleanolic Acid; Phytotherapy; RNA, Messenger; Saponins; Signal Transduction; Stevia; Tea

Our previous study showed that dietary stevioside supplementation could alleviate intestinal mucosal damage induced by lipopolysaccharide (LPS) through its anti-inflammatory and antioxidant effects in broiler chickens. However, it remains unknown whether feeding stevioside to breeder hens could exert similar biological functions in their offspring. The present study aimed to investigate whether maternal dietary stevioside supplementation could prevent LPS-induced intestinal mucosal damage and alteration of gut microbiota in chicken offspring. A total of 120 Jinmao yellow-feathered breeder hens were fed a basal diet (CON) or a 250 mg kg

Topics: Animal Feed; Animals; Anti-Inflammatory Agents; Antioxidants; Chickens; Cytokines; Diet; Dietary Supplements; Diterpenes, Kaurane; Female; Gastrointestinal Microbiome; Gene Expression Regulation; Glucosides; Inflammation; Intestinal Mucosa; Intestines; Lipopolysaccharides; Male; RNA, Ribosomal, 16S

Adjuvant arthritis is a chronic, autoimmune and inflammatory disorder of the joints. The occurrence of disorder causes a severe damage to the connective tissue eventually leading to progressive physical disability and eventual death. The recent years of evidence suggests the anti-inflammatory properties of stevioside, a diterpene glycoside. However, the effect of stevioside against adjuvant arthritis, a chronic inflammatory disorder is not known. Hence, the present study was designed to study the effect of stevioside against Freund's complete adjuvant induced arthritis model in rats. The acute anti-inflammatory effect of stevioside also studied by employing carrageenan-induced paw oedema model in rats. The biochemical markers, haematological parameters, lipid peroxidation, myeloperoxidase activity, lipoxygenase activity, the levels of PGE2 and pro-inflammatory (TNF-α, IL-6 & IL-1β) and anti-inflammatory cytokine (IL-10) were analysed. The protein expression of NF-κB (p65) COX-2 and iNOS in paw tissues were estimated by western blotting. Stevioside treatment significantly ameliorates the adjuvant induced arthritic scoring, histological alterations, paw volume, elevation of biochemical (AST, ALT, ALP and glucose levels) and haematological (haemoglobin, differential and platelet count) parameters and restored the endogenous anti-oxidant (SOD, CAT, GSH and GST) activities. Treatment with stevioside also significantly prevented the adjuvant induced elevation of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), pro-inflammatory protein expressions (iNOS, COX-2, NF-κB (p65) and pIκB/IκB ratio), prevented the increase in myeloperoxidase activity and significantly restored the anti-inflammatory (IL-10) cytokine level in paw tissues. Collectively, our findings suggest that stevioside may serve as anti-inflammatory agent and could serve as a potential adjunct therapeutic option in treating adjuvant arthritis.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arthritis, Experimental; Biomarkers; Cytokines; Disease Models, Animal; Diterpenes, Kaurane; Freund's Adjuvant; Glucosides; Inflammation; Rats; Rats, Sprague-Dawley

Extracts derived from the leaves of the stevia plant (stevioside) are commonly used as sweeteners for humans and horses. Stevioside appears to be safe for human consumption, including for individuals with insulin dysregulation. In the horse, the safety or metabolic effects of stevioside on normal animals or on those with metabolic dysfunction are unknown. Furthermore, the inflammatory response to a glycemic challenge or to stevioside in horses is not well defined. Therefore, the objective of this study was to measure the effects of stevioside and a glycemic challenge on insulin, glucose, and inflammatory responses in horses with a common metabolic dysfunction (equine metabolic syndrome or EMS) compared with non-EMS controls. To accomplish this, 15 horses were selected; 8 EMS and 7 age-matched controls. An oral sugar test was performed using Karo corn syrup (karo) or stevioside in a random crossover design. Horses were given 0.15 mL/kg body weight of karo or its equivalent grams of sugar in stevia dissolved in water. Blood samples were collected by jugular venipuncture before administration of either stevia or karo and at 60 and 240 min after administration. Serum was used for glucose and insulin determination and plasma for isolation of peripheral blood mononuclear cells (PBMCs) for inflammatory cytokine analysis via flow cytometry and reverse transcription PCR (RT-PCR). Stevia appeared to stimulate lower glycemic and insulinemic responses when compared to karo, in particular in EMS horses. EMS and control horses had inverse inflammatory responses to administration of either stevia or karo with EMS horses having a proinflammatory response (P ≤ 0.05). These data provide evidence as to why horses with EMS may be predisposed to developing laminitis, potentially as a result of an exaggerated inflammatory response to glycemic and insulinemic responses. Furthermore, the data provide new avenues for exploring mechanisms behind the syndrome, in particular when using a glycemic challenge.

Topics: Animals; Blood Glucose; Case-Control Studies; Diterpenes, Kaurane; Glucosides; Horse Diseases; Horses; Inflammation; Insulin; Metabolic Syndrome; Sweetening Agents

Stevioside is a natural non-caloric sweetener isolated from Stevia rebaudiana Bertoni leaves. We have proposed its effect on attenuation of tumour necrosis factor α (TNF-α) and interleukin 1β (IL-1β) release in lipopolysaccharide (LPS)-stimulated monocytes. In this study, the anti-inflammatory and immunomodulatory activities of stevioside and its metabolite, steviol, on human colon carcinoma cell line (Caco-2) were evaluated.. Stevioside and steviol, in the doses used in this study, had no cytotoxicity on Caco-2 cells. Anti-inflammatory activities of these two compounds were observed by potentially suppressed LPS-mediated TNF-α, IL-1β and IL-6 release. In addition, stevioside and steviol showed immunomodulatory effects on IκBα activation and nuclear factor kappa B (NF-κB) suppression in western blotting.. Stevioside and steviol attenuate LPS-induced pro-inflammatory cytokine productions by affecting cytokine gene expression via IκBα/NF-κB signalling pathway.

Topics: Anti-Inflammatory Agents; Caco-2 Cells; Colon; Cytokines; Diterpenes, Kaurane; Epithelial Cells; Gene Expression; Glucosides; Humans; I-kappa B Proteins; Immunologic Factors; Inflammation; Inflammation Mediators; Intestinal Mucosa; Lipopolysaccharides; NF-kappa B; NF-KappaB Inhibitor alpha; Phytotherapy; Plant Extracts; Signal Transduction; Stevia

Stevioside, a diterpene glycoside component of Stevia rebaudiana, has been known to exhibit anti-inflammatory properties. To evaluate the effect and the possible mechanism of stevioside in lipopolysaccharide (LPS)-induced acute lung injury, male BALB/c mice were pretreated with stevioside or dexamethasone 1 h before intranasal instillation of LPS. Seven hours later, tumor necrosis factor-α, interleukin-1β, and interleukin-6 in bronchoalveolar lavage fluid (BALF) were measured by using enzyme-linked immunosorbent assay. The number of total cells, neutrophils, and macrophages in the BALF were also determined. The right lung was excised for histological examination and analysis of myeloperoxidase activity and nitrate/nitrite content. Cyclooxygenase 2 (COX-2), inducible NO synthase (iNOS), nuclear factor-kappa B (NF-κB), inhibitory kappa B protein were detected by western blot. The results showed that stevioside markedly attenuated the LPS-induced histological alterations in the lung. Stevioside inhibited the production of pro-inflammatory cytokines and the expression of COX-2 and iNOS induced by LPS. In addition, not only was the wet-to-dry weight ratio of lung tissue significantly decreased, the number of total cells, neutrophils, and macrophages in the BALF were also significantly reduced after treatment with stevioside. Moreover, western blotting showed that stevioside inhibited the phosphorylation of IκB-α and NF-κB caused by LPS. Taken together, our results suggest that anti-inflammatory effect of stevioside against the LPS-induced acute lung injury may be due to its ability of inhibition of the NF-κB signaling pathway. Stevioside may be a promising potential therapeutic reagent for acute lung injury treatment.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Cell Count; Cyclooxygenase 2; Dexamethasone; Diterpenes, Kaurane; Glucosides; I-kappa B Kinase; Inflammation; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Lung; Macrophages; Male; Mice; Mice, Inbred BALB C; Neutrophils; NF-kappa B; Nitrates; Nitric Oxide Synthase Type II; Nitrites; Peroxidase; Phosphorylation; Random Allocation; Signal Transduction; Tumor Necrosis Factor-alpha

Accumulating evidence suggests that adipose tissue is the main source of pro-inflammatory molecules that predispose individuals to insulin resistance. Stevioside (SVS) is a widely used sweetener with multiple beneficial effects for diabetic patients. In this study, we investigated the effect of SVS on insulin resistance and the pro-inflammatory state of adipose tissue in mice fed with a high-fat diet (HFD). Oral administration of SVS for 1month had no effect on body weight, but it significantly improved fasting glucose, basal insulin levels, glucose tolerance and whole body insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of several inflammatory cytokines in adipose tissue, including TNF-α, IL6, IL10, IL1β, KC, MIP-1α, CD11b and CD14. Moreover, macrophage infiltration in adipose tissue was remarkably reduced by SVS. Finally, SVS significantly suppressed the nuclear factor-kappa b (NF-κB) signaling pathway in adipose tissue. Collectively, these results suggested that SVS may ameliorate insulin resistance in HFD-fed mice by attenuating adipose tissue inflammation and inhibiting the NF-κB pathway.

Topics: Adipose Tissue; Animals; Cytokines; Diet, High-Fat; Diterpenes, Kaurane; Down-Regulation; Glucose Tolerance Test; Glucosides; Inflammation; Insulin; Insulin Resistance; Macrophages; Male; Mice; Mice, Inbred C57BL; NF-kappa B; RNA, Messenger; Sweetening Agents

Stevioside, a diterpene glycoside isolated from Stevia rebaudiana, has been reported to have anti-inflammatory properties. However, the underlying molecular mechanisms are not well understood. The objective of this study was to investigate the molecular mechanism of stevioside in modifying lipopolysaccharide (LPS)-induced signal pathways in RAW264.7 cells. RAW264.7 cells were stimulated with LPS in the presence or absence of stevioside. The expression of pro-inflammatory cytokines was determined by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction. Nuclear factor-κB (NF-κB), inhibitory kappa B (IκBα) protein, p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) were determined by western blot. The results showed that stevioside dose-dependently inhibited the expression of tumor necrosis factor-α, interleukin-6, and interleukin-1β in LPS-stimulated RAW264.7 cells. Western blot analysis showed that stevioside suppressed LPS-induced NF-κB activation, IκBa degradation, phosphorylation of ERK, JNK, and P38. Our results suggest that stevioside exerts an anti-inflammatory property by inhibiting the activation of NF-κB and mitogen-activated protein kinase signaling and the release of proinflammatory cytokines. These findings suggest that stevioside may be a therapeutic agent against inflammatory diseases.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Line; Cell Survival; Diterpenes, Kaurane; Down-Regulation; Glucosides; I-kappa B Proteins; Inflammation; Interleukin-1beta; Interleukin-6; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; Macrophages; MAP Kinase Signaling System; Mice; Mitogen-Activated Protein Kinases; NF-kappa B; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Tumor Necrosis Factor-alpha