Syzygium aromaticum Reduces Diabetes-induced Glucotoxicity via the NRF2/Glo1 Pathway.

Advanced glycation end products and methylglyoxal are known to show increased levels in diabetic conditions and induce diverse metabolic disorders. However, the antiglycation ability of the bark of Syzygium aromaticum is not yet studied. In this study, we determined the inhibitory effects of S. aromaticum on AGE formation. Moreover, S. aromaticum showed breakage and inhibitory ability against the formation of AGE-collagen crosslinks. In SV40 MES13 cells, treatment with the S. aromaticum extract significantly ameliorated MG-induced oxidative stress as well as cytotoxicity. Furthermore, in the S. aromaticum extract-treated group, there was a reduction in levels of several diabetic markers, such as blood glucose, kidney weight, and urinary albumin to creatinine ratio in streptozotocin-induced diabetic rats. Treatment with the S. aromaticum extract significantly increased the expression of nuclear factor erythroid 2-related factor 2, a transcription factor involved in the expression of antioxidant enzymes. Moreover, the treatment significantly upregulated the expression of glyoxalase 1 and downregulated the expression of receptor for AGEs. These results suggest that the S. aromaticum extract might ameliorate diabetes-induced renal damage by inhibiting the AGE-induced glucotoxicity and oxidative stress through the Nrf2/Glo1 pathway.

Isobavachalcone attenuates myotube atrophy induced by TNF-α through muscle atrophy F-box signaling and the nuclear factor erythroid 2-related factor 2 cascade.

Skeletal muscle atrophy is a condition characterized by damaged muscle fibers and reduced numbers of muscle cells due to various causes. Muscle atrophy is associated with chronic diseases, such as heart failure, diabetes, and aging-related diseases. Isobavachalcone (IBC) is a flavonoid found in various foods and natural products, and studies have investigated its diverse effects, including its neuroprotective and anticancer effects. However, no studies have evaluated the effects of IBC on muscle atrophy. Thus, in this study, we assessed the effects of IBC on prevention of muscle atrophy. To evaluate the preventive effects of IBC on muscle atrophy, we used C2C12 myoblasts and induced muscle atrophy by tumor necrosis factor (TNF)-α. IBC regulated the expression levels of muscle atrophy F-box and muscle RING finger-1 in response to damaged muscle cells, thereby restoring the expression of myosin heavy chain and myogenin. Moreover, IBC regulated the phosphorylation of the nuclear factor-κB and p38 and upregulated the expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1, which are involved in regulating oxidative stress. Our results indicated that IBC acted to relieve TNF-α-induced skeletal muscle atrophy by regulating the factors related to inflammation and oxidative stress.

Spatholobus suberectus Ameliorates Diabetes-Induced Renal Damage by Suppressing Advanced Glycation End Products in db/db Mice.

Spatholobus suberectus (SS) is a medicinal herb commonly used in Asia to treat anemia, menoxenia and rheumatism. However, its effect of diabetes-induced renal damage and mechanisms of action against advanced glycation end-products (AGEs) are unclear. In this study, we evaluated the effects of SS on diabetes-induced renal damage and explored the possible underlying mechanisms using db/db type 2 diabetes mice. db/db mice were administered SS extract (50 mg/kg) orally for 6 weeks. SS-treated group did not change body weight, blood glucose and glycated hemoglobin (HbA1c) levels. However, SS treatment reversed diabetes-induced dyslipidemia and urinary albumin/creatinine ratio in db/db mice. Moreover, SS administration showed significantly increased protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which is a transcription factor for antioxidant enzyme. SS significantly upregulated glyoxalase 1 (Glo1) and NADPH quinine oxidoreductase 1 (NQO1) expression but reduced CML accumulation and downregulated receptor for AGEs (RAGE). Furthermore, SS showed significant decrease of periodic acid⁻Schiff (PAS)-positive staining and AGEs accumulation in histological and immunohistochemical analyses of kidney tissues. Taken together, we concluded that SS ameliorated the renal damage by inhibiting diabetes-induced glucotoxicity, dyslipidemia and oxidative stress, through the Nrf2/antioxidant responsive element (ARE) stress-response system.

Neochlorogenic Acid Inhibits Lipopolysaccharide-Induced Activation and Pro-inflammatory Responses in BV2 Microglial Cells.

Microglia is the resident innate immune cells that sense pathogens and tissue injury in the central nervous system. Microglia becomes activated in response to injury, infection, and other stimuli that threaten neuronal survival. Microglia activation plays an important role in neurodegenerative diseases. Neochlorogenic acid (NCA) is a natural polyphenolic compound found in dried fruits and other plants. Although previous studies have shown that phenolic acids including NCA have outstanding antioxidant, antibacterial, antiviral, and antipyretic activities, there has not yet been investigated for anti-inflammatory effects. Therefore, for the first time we have examined the potential of NCA to inhibit microglial activation and pro-inflammatory responses in the brain. We found that lipopolysaccharide-induced inducible nitric oxide synthase, and cyclooxygenase-2 expression, and nitric oxide formation was suppressed by NCA in a dose-dependent manner in BV2 microglia. NCA also inhibited the production of pro-inflammatory mediators, tumor necrosis factor-α and interleukin-1 beta. Furthermore, phosphorylated nuclear factor-kappa B p65 and p38 mitogen-activated protein kinase activation were blocked by NCA. Taken together, these results suggest that NCA exerts neuroprotective effects through the inhibition of pro-inflammatory pathways in activated microglia.

Regulatory Effect of 25-hydroxyvitamin D3 on Nitric Oxide Production in Activated Microglia.

Microglia are activated by inflammatory and pathophysiological stimuli in neurodegenerative diseases, and activated microglia induce neuronal damage by releasing cytotoxic factors like nitric oxide (NO). Activated microglia synthesize a significant amount of vitamin D3 in the rat brain, and vitamin D3 has an inhibitory effect on activated microglia. To investigate the possible role of vitamin D3 as a negative regulator of activated microglia, we examined the effect of 25-hydroxyvitamin D3 on NO production of lipopolysaccharide (LPS)-stimulated microglia. Treatment with LPS increased the production of NO in primary cultured and BV2 microglial cells. Treatment with 25-hydroxyvitamin D3 inhibited the generation of NO in LPS-activated primary microglia and BV2 cells. In addition to NO production, expression of 1-α-hydroxylase and the vitamin D receptor (VDR) was also upregulated in LPS-stimulated primary and BV2 microglia. When BV2 cells were transfected with 1-α-hydroxylase siRNA or VDR siRNA, the inhibitory effect of 25-hydroxyvitamin D3 on activated BV2 cells was suppressed. 25-Hydroxyvitamin D3 also inhibited the increased phosphorylation of p38 seen in LPS-activated BV2 cells, and this inhibition was blocked by VDR siRNA. The present study shows that 25-hydroxyvitamin D3 inhibits NO production in LPS-activated microglia through the mediation of LPS-induced 1-α-hydroxylase. This study also shows that the inhibitory effect of 25-hydroxyvitamin D3 on NO production might be exerted by inhibiting LPS-induced phosphorylation of p38 through the mediation of VDR signaling. These results suggest that vitamin D3 might have an important role in the negative regulation of microglial activation.

Correction: The emerging role of medical foods and therapeutic potential of medical food-derived exosomes.

[This corrects the article DOI: 10.1039/D3NA00649B.].

Proteomic analysis of primary cultured rat cortical neurons in chemical ischemia.

To elucidate the molecular events involved in early ischemic neuronal death, we performed two-dimensional proteome profiling of primary cultures of rat cortical neurons following chemical ischemia induced by the administration of sodium azide under glucose-free conditions. Using a lactic dehydrogenase assay and Western blot analysis of dephosporylation of the voltage-gated potassium channel Kv2.1, we determined duration of chemical ischemia of 2 h to be the relevant time-point for early ischemic neuronal death. Sixty-one proteins were differentially expressed, and 26 different proteins were identified by MALDI-TOF with Mascot database searching. The proteome data indicated that chemical ischemia altered the expression of 20 proteins that are involved in stress response/chaperone, brain development, cytoskeletal/structural proteins, metabolic enzymes, and calcium ion homeostasis. Western blotting and immunocytochemical studies of the 6-most functionally significant proteins showed that, in the ischemia-treated group, the expression of glucose-related protein 78, heat shock protein 90 alpha, and α-enolase was significantly increased, while the expression of inositol triphosphate receptor 1 and ATP synthase beta subunit was decreased. In addition, the expression of dihydropyrimidinase-like 3 showed a truncated pattern in the ischemia group. The changes in the expression of these proteins might be significant indicators of early ischemic neuronal death.

Sanguisorbae radix protects against 6-hydroxydopamine-induced neurotoxicity by regulating NADPH oxidase and NF-E2-related factor-2/heme oxygenase-1 expressions.

6-Hydroxydopamine (6-OHDA) produces neuronal cell damage by generating reactive oxygen species (ROS). The major mechanisms of protection against ROS-induced stress are inhibiting expression of ROS generating genes such as NADPH oxidase (NOX) and increasing expression of endogenous antioxidant genes such as heme oxygenase-1 (HO-1). This study investigated whether a standardized Sanguisorbae Radix extract (SRE), a medical herb commonly used in Asian traditional medicine, has a protective effect on 6-OHDA-induced cell toxicity by regulating ROS in SH-SY5Y cells. SRE at 10 and 50 µg/mL significantly reduced 6-OHDA-induced cell damage dose dependently in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and by Hoechst 33342 staining. SRE increased the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X ratio and decreased cytochrome C release and caspase-3 activity. SRE also abolished 6-OHDA-induced ROS by inhibiting NOX expression and by inducing HO-1 expression via NF-E2-related factor-2 activation. Taken together, these results demonstrate that SRE has protective effects against 6-OHDA-induced cell death by regulating ROS in SH-SY5Y cells.

Borneol alleviates oxidative stress via upregulation of Nrf2 and Bcl-2 in SH-SY5Y cells.

CONTEXT: The ß-amyloid (Aß) peptide aggregation with accompanying oxidative stress plays the major role in the pathogenesis of Alzheimer's disease (AD). Some natural compounds, including borneol, shed promising light on AD treatment. OBJECTIVE: The present study was designed to investigate the antioxidative, antiapoptotic effects, and neuroprotection of borneol in human neuroblastoma cells (SH-SY5Y). MATERIALS AND METHODS: Oxidative stress was induced by administering 50 µM Aß into SH-SY5Y cells. Neuroprotective effect of commercially available borneol was examined by determining cell viability with the MTT assay. Intracellular reactive oxygen species (ROS) generation was measured using a fluorometer with further examination of heme oxygenase-1 (HO-1) and nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) expression. Apoptosis was examined by measuring the ratio of B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax). RESULTS: Our data indicated that Aß-induced cell cytotoxicity was inhibited by 100 µM of (-) and (+) borneol treatment. Treatment of borneol significantly decreased ROS generation (P < 0.01). The expression of HO-1 and nuclear translocation of Nrf2 were increased by Aß treatment. This nuclear translocation of Nrf2 was further increased by administration of borneol. Compared with the Aß treated group, the (+) borneol treated group significantly increased Bcl-2 expression with decreased expression of Bax. DISCUSSION AND CONCLUSION: Borneol protected SH-SY5Y cells against Aß-induced toxicity, exerted an antioxidative effect and suppressed apoptosis. It increases our knowledge about neuroprotective mechanism of borneol, and it is hopeful to be a candidate compound for developing therapeutic drug for the prevention and treatment of AD and other Aß-related neurodegenerative diseases.

Expression and activity of the na-k ATPase in ischemic injury of primary cultured astrocytes.

Astrocytes are reported to have critical functions in ischemic brain injury including protective effects against ischemia-induced neuronal dysfunction. Na-K ATPase maintains ionic gradients in astrocytes and is suggested as an indicator of ischemic injury in glial cells. Here, we examined the role of the Na-K ATPase in the pathologic process of ischemic injury of primary cultured astrocytes. Chemical ischemia was induced by sodium azide and glucose deprivation. Lactate dehydrogenase assays showed that the cytotoxic effect of chemical ischemia on astrocytes began to appear at 2 h of ischemia. The expression of Na-K ATPase α1 subunit protein was increased at 2 h of chemical ischemia and was decreased at 6 h of ischemia, whereas the expression of α1 subunit mRNA was not changed by chemical ischemia. Na-K ATPase activity was time-dependently decreased at 1, 3, and 6 h of chemical ischemia, whereas the enzyme activity was temporarily recovered to the control value at 2 h of chemical ischemia. Cytotoxicity at 2 h of chemical ischemia was significantly blocked by reoxygenation for 24 h following ischemia. Reoxygenation following chemical ischemia for 1 h significantly increased the activity of the Na-K ATPase, while reoxygenation following ischemia for 2 h slightly decreased the enzyme activity. These results suggest that the critical time for ischemia-induced cytotoxicity of astrocytes might be 2 h after the initiation of ischemic insult and that the increase in the expression and activity of the Na-K ATPase might play a protective role during ischemic injury of astrocytes.

The emerging role of medical foods and therapeutic potential of medical food-derived exosomes.

Medical food is consumed for the purpose of improving specific nutritional requirements or disease conditions, such as inflammation, diabetes, and cancer. It involves partial or exclusive feeding for fulfilling unique nutritional requirements of patients and is different from medicine, consisting of basic nutrients, such as polyphenols, vitamins, sugars, proteins, lipids, and other functional ingredients to nourish the patients. Recently, studies on extracellular vesicles (exosomes) with therapeutic and drug carrier potential have been actively conducted. In addition, there have been attempts to utilize exosomes as medical food components. Consequently, the application of exosomes is expanding in different fields with increasing research being conducted on their stability and safety. Herein, we introduced the current trends of medical food and the potential utilization of exosomes in them. Moreover, we proposed Medi-Exo, a exosome-based medical food. Furthermore, we comprehensively elucidate various disease aspects between medical food-derived exosomes (Medi-Exo) and therapeutic natural bionanocomposites. This review highlights the therapeutic challenges regarding Medi-Exo and its potential health benefits.

Chronic hyperosmotic stress converts GABAergic inhibition into excitation in vasopressin and oxytocin neurons in the rat.

In mammals, the increased secretion of arginine-vasopressin (AVP) (antidiuretic hormone) and oxytocin (natriuretic hormone) is a key physiological response to hyperosmotic stress. In this study, we examined whether chronic hyperosmotic stress weakens GABA(A) receptor-mediated synaptic inhibition in rat hypothalamic magnocellular neurosecretory cells (MNCs) secreting these hormones. Gramicidin-perforated recordings of MNCs in acute hypothalamic slices prepared from control rats and ones subjected to the chronic hyperosmotic stress revealed that this challenge not only attenuated the GABAergic inhibition but actually converted it into excitation. The hyperosmotic stress caused a profound depolarizing shift in the reversal potential of GABAergic response (E(GABA)) in MNCs. This E(GABA) shift was associated with increased expression of Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) in MNCs and was blocked by the NKCC inhibitor bumetanide as well as by decreasing NKCC activity through a reduction of extracellular sodium. Blocking central oxytocin receptors during the hyperosmotic stress prevented the switch to GABAergic excitation. Finally, intravenous injection of the GABA(A) receptor antagonist bicuculline lowered the plasma levels of AVP and oxytocin in rats under the chronic hyperosmotic stress. We conclude that the GABAergic responses of MNCs switch between inhibition and excitation in response to physiological needs through the regulation of transmembrane Cl(-) gradients.

Inhibitory effect of sea buckthorn extracts on advanced glycation endproduct formation.

This study shows the inhibitory effect of sea buckthorn (Hippophae rhamnoides L.) extracts, sea buckthorn leaf (HRL) and berry (HRB), on the formation of advanced glycation endproducts (AGEs), closely linked to diverse disease. In vitro assay revealed the superior inhibitory effect of HRL on the AGEs formation and AGEs-induced collagen crosslinking compared with that of HRB. Ultra-performance liquid chromatography-mass spectrometry results revealed that HRL displays a higher inhibition efficiency on the AGEs formation at 30 AGEs binding sites in bovine serum albumin than HRB. The high concentration of 3-sophoroside-7-rhamnoside in HRL compared with that in HRB may result in the strong inhibitory effect of HRL compared with that of HRB. HRL also exhibited significantly higher ABTS and DPPH radical scavenging activities than HRB. Overall, this study demonstrated that HRL has excellent potential as a dietary agent for controlling various diseases mediated by AGEs and oxidative stress.

Lactococcus lactis KF140 Reduces Dietary Absorption of Nε - (Carboxymethyl)lysine in Rats and Humans via ß-Galactosidase Activity.

Background and Aims: Excessive intake of advanced glycation end products (AGEs), which are formed in foods cooked at high temperatures for long periods of time, has negative health effects, such as inflammatory responses and oxidative stress. Nε-(Carboxymethyl)lysine (CML) is one of the major dietary AGEs. Given their generally recognized as safe status and probiotic functionalities, lactic acid bacteria may be ideal supplements for blocking intestinal absorption of food toxicants. However, the protective effects of lactic acid bacteria against dietary AGEs have not been fully elucidated. Materials and Methods: We investigated the effect of treatment with Lactococcus lactis KF140 (LL-KF140), which was isolated from kimchi, on the levels and toxicokinetics of CML. The CML reduction efficacies of the Lactococcus lactis KF140 (LL-KF140), which was isolated from kimchi, were conducted by in vitro test for reducing CML concentration of the casein-lactose reaction product (CLRP) and in vivo test for reducing serum CML level of LL-KF140 administered rats at 2.0 × 108 CFU/kg for14 days. In addition, 12 volunteers consuming LL-KF140 at 2.0 × 109 CFU/1.5 g for 26 days were determined blood CML concentration and compared with that before intake a Parmesan cheese. Results: Administration of LL-KF140 reduced serum CML levels and hepatic CML absorption in rats that were fed a CML-enriched product. In a human trial, the intake of LL-KF140 prevented increases in the serum levels of CML and alanine aminotransferase after consumption of a CML-rich cheese. LL-KF140 was determined to presence in feces through metagenome analysis. Furthermore, ß-galactosidase, one of the L. lactis-produced enzymes, inhibited the absorption of CML and reduced the levels of this AGE, which suggests an indirect inhibitory effect of LL-KF140. This study is the first to demonstrate that an L. lactis strain and its related enzyme contribute to the reduction of dietary absorption of CML.

Ishige okamurae Ameliorates Methylglyoxal-Induced Nephrotoxicity via Reducing Oxidative Stress, RAGE Protein Expression, and Modulating MAPK, Nrf2/ARE Signaling Pathway in Mouse Glomerular Mesangial Cells.

Advanced glycation end-products (AGEs) such as methylglyoxal (MGO) play a vital role in the pathogenesis of nephropathy, a diabetic complication. In the present study, we evaluated the anti-glycation and renal protective properties of Ishige okamurae extract (IOE) against AGE-induced oxidative stress. HPLC analysis confirmed that bioactive phlorotannins such as diphlorethohydroxycarmalol and ishophloroglucin A are predominantly present in IOE. IOE showed strong anti-glycation activities via inhibition of AGE formation, inhibition of AGE-protein cross-linking, and breaking of AGE-protein cross-links. In addition, in vitro studies using mesangial cells demonstrated that IOE effectively suppressed intracellular reactive oxygen species production, intracellular MGO accumulation, and apoptotic cell death by MGO-induced oxidative stress, in addition to regulating the expression of proteins involved in the receptor for AGEs and nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements (ARE) signaling pathways. Therefore, IOE can serve as a natural therapeutic agent for the management of AGE-related nephropathy.

Ischemia-activated microglia induces neuronal injury via activation of gp91phox NADPH oxidase.

Although glial cells play a major role in the pathogenesis of many neurological diseases by exacerbating neuronal and non-neuronal cell death, the mechanisms involved are unclear. We examined the effects of microglia-(MCM) or astrocyte-(ACM) conditioned media obtained by chemical ischemia on the neuronal injury in SH-SY5Y cells. Chemical ischemia was induced by the treatment with NaN(3) and 2-deoxy-d-glucose for 2h. MCM-treated SH-SY5Y cells showed reduced the viability, increased caspase-3 activity, decreased Bcl-2/Bax ratio, and increased cytochrome c release, increased inflammatory cytokines, and increased reactive oxygen species (ROS) generation. MCM also increased gp91phox nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which was inhibited by NADPH oxidase inhibitor, apocynin, and gp91phox siRNA. However, ACM did not show any significant changes. The results suggest that microglia activated by ischemic insult may increase reactive oxygen species generation via activation of gp91phox NADPH oxidase, resulting in neuronal injury.

Coffee consumption promotes skeletal muscle hypertrophy and myoblast differentiation.

Coffee is a widely consumed beverage worldwide and is believed to help prevent the occurrence of various chronic diseases. However, the effect of coffee on skeletal muscle hypertrophy, differentiation and the mechanisms of action responsible have remained unclear. To investigate the effect of coffee on skeletal muscle hypertrophy, mice were fed a normal diet or a normal diet supplemented with 0.3% coffee or 1% coffee. Coffee supplementation was observed to increase skeletal muscle hypertrophy, while simultaneously upregulating protein expression of total MHC, MHC2A, and MHC2B in quadricep muscle. Myostatin expression was also attenuated, and IGF1 was upregulated with subsequent phosphorylation of Akt and mTOR, while AMPK phosphorylation was attenuated. Coffee also increased the grip strength and PGC-1α protein expression, and decreased the expressions of TGF-ß and myostatin in tricep muscle. Coffee activated the MKK3/6-p38 pathway and upregulated PGC-1α, which may play a role in promoting myogenic differentiation and myogenin expression in C2C12 cells. These results suggest that coffee increases skeletal muscle function and hypertrophy by regulating the TGF-ß/myostatin - Akt - mTORC1.

Eucommia ulmoides Ameliorates Glucotoxicity by Suppressing Advanced Glycation End-Products in Diabetic Mice Kidney.

Eucommia ulmoides Oliv. (EU), also known as Du-Zhong, is a medicinal herb commonly used in Asia to treat hypertension and diabetes. Despite evidence of the protective effects of EU against diabetes, its precise effects and mechanisms of action against advanced glycation end-products (AGEs) are unclear. In this study, we evaluated the effects of EU on AGEs-induced renal disease and explored the possible underlying mechanisms using streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice received EU extract (200 mg/kg) orally for 6 weeks. EU treatment did not change blood glucose and glycated hemoglobin (HbA1c) levels in diabetic mice. However, the EU-treated group showed a significant increase in the protein expression and activity of glyoxalase 1 (Glo1), which detoxifies the AGE precursor, methylglyoxal (MGO). EU significantly upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression but downregulated that of receptor for AGE (RAGE). Furthermore, histological and immunohistochemical analyses of kidney tissue showed that EU reduced periodic acid-Schiff (PAS)-positive staining, AGEs, and MGO accumulation in diabetic mice. Based on these findings, we concluded that EU ameliorated the renal damage in diabetic mice by inhibiting AGEs formation and RAGE expression and reducing oxidative stress, through the Glo1 and Nrf2 pathways.

(2R,3S,2″R,3″R)-Manniflavanone Protects Proliferating Skeletal Muscle Cells against Oxidative Stress and Stimulates Myotube Formation.

We investigated the antioxidative properties of (2R,3S,2″R,3″R)-manniflavanone (MF) using in vitro assays and examined its effects on myogenesis and lactate-induced oxidative stress in C2C12 cells. MF was purified from Garcinia buchananii stem bark. H2O2 and oxygen radical absorbance capacity assays demonstrated that MF is a powerful antioxidant. This finding was supported by diphenylpicrylhydrazine radical scavenging activity of MF. MF was less cytotoxic to C2C12 cells compared to ascorbic acid and myricetin. Moreover, MF accelerated myotube formation in the differentiated C2C12 cells by up-regulating myogenic proteins such as MyoG and myosin heavy chain. Furthermore, MF rescued late differentiation of myoblast suppressed by lactate treatment and up-regulated the expression levels of Nrf2 in lactate-induced oxidative stress, indicating that MF stimulates antioxidative activity inside C2C12 cells. Collectively, MF is a potent antioxidant with a higher safety profile than ascorbic acid and myricetin. It reduces oxidative stress-induced delaying of skeletal muscle differentiation by scavenging reactive oxygen species and regulating myogenic proteins factors.

15,16-dihydrotanshinone I suppresses the activation of BV-2 cell, a murine microglia cell line, by lipopolysaccharide.

Microglial activation has been implicated in neurodegenerative diseases. Therefore, inhibition of inflammation mediated by microglia is a strategy in neurodegenerative disease therapy. In this study, we isolated cryptotanshinone and 15,16-dihydrotanshinone I from Salvia miltiorrhiza, a traditional Korean herb medicine, by bioactivity-guided fractionation based on inhibitory effect on nitric oxide in a lipopolysaccharide-stimulated BV-2 cells, a murine microglial cell line. 15,16-Dihydotanshinoe I suppressed the expression of not only inducible nitric oxide synthase but also of interleukin-1beta, tumor necrosis factor-alpha, and of TNF-alpha converting enzyme.