Inflammation is an important immune response to pathogen invasion, but excessive inflammation leads to tissue injury and even cytokine storm. Therefore, proper response is needed depending on the ...intensity of the infection. Ras guanine nucleotide releasing protein 3 (RasGRP3) is a regulator of the TLR-mediated response. In low-intensity inflammation, it negatively regulates production of pro-inflammatory cytokines, especially IL-6. Citri Reticulatae Pericarpium, the peel of Citrus reticulata Blanco, is a major medicinal herb in Korean medicine. The present study aims to investigate whether the Citri Reticulatae Pericarpium extract (CRE) has immunomodulatory activity using the Raw264.7 macrophage. Also, we investigated the effect of CRE on RasGRP3 expression. In the present study, CRE reduced IL-6 production in the low-LPS environment (1 ng/mL) and did not in the high-LPS environment (100 ng/mL). The suppression of IL-6 production in the low-LPS environment (1 ng/mL) was abolished after the pretreatment of RasGRP3 siRNA. The reduced RasGRP3 protein content by 100 ng/mL LPS treatment was increased by CRE treatment. Additionally, nobiletin, a major component of CRE showed a suppressive effect on IL-6 production in the low-LPS environment (1 ng/mL). The present results suggest that CRE alleviates inflammatory response via activating RasGRP3 expression in low-intensity inflammation.
The whitening effect of reducing skin pigmentation is one of the most important goals of cosmetics. The purpose of this study was to determine whether
extract and its fractions have potential as ...natural skin-lightening agents. Initially, we screened various fractions of
extract using an in vitro antioxidant assay. Then, the inhibitory effects of
extract and its fraction on melanogenesis and the related mechanisms were investigated in B16F1 melanoma cells. The results showed that the ethyl acetate fraction (EF) from
extract markedly inhibited melanin synthesis in a dose-dependent manner at non-toxic concentrations. Furthermore, EF downregulated both the protein and mRNA levels of tyrosinase, which is a specific enzyme that catalyzes the conversion of tyrosine into melanin. We also found that EF decreased the microphthalmia-associated transcription factor (MITF) at the protein and mRNA levels. EF increased the phosphorylation of ERK and suppressed the phosphorylation of JNK and p38 in ɑ-MSH-induced B16F1 cells. These results indicate that EF can regulate the MAPK pathway. In addition, EF has an anti-melanogenic effect via the downregulation of intracellular cyclic-AMP (cAMP). Nineteen major compounds of EF were identified using LC-MS/MS. Taken together, these results suggest that EF may be a potential anti-melanogenic agent for use in skin-whitening cosmetics and in topical treatments for hyperpigmentation disorders.
Chitin is a natural polysaccharide of major importance. This biopolymer is synthesized by an enormous number of living organisms; considering the amount of chitin produced annually in the world, it ...is the most abundant polymer after cellulose. The most important derivative of chitin is chitosan, obtained by partial deacetylation of chitin under alkaline conditions or by enzymatic hydrolysis. Chitin and chitosan are known to have important functional activities but poor solubility makes them difficult to use in food and biomedicinal applications. Chitooligosaccharides (COS) are the degraded products of chitosan or chitin prepared by enzymatic or chemical hydrolysis of chitosan. The greater solubility and low viscosity of COS have attracted the interest of many researchers to utilize COS and their derivatives for various biomedical applications. In light of the recent interest in the biomedical applications of chitin, chitosan, and their derivatives, this review focuses on the preparation and biological activities of chitin, chitosan, COS, and their derivatives.
Activation of microglial cells by intrinsic or extrinsic insult causes neuroinflammation, a common phenomenon in neurodegenerative diseases. Prevention of neuroinflammation may ameliorate many ...neurodegenerative disease progressions. Dioscorea nipponica Makino (DN) extract can alleviate muscular atrophy and inflammatory diseases; however, the efficacy and mechanism of action in microglial cells remain unknown. The current study investigates the possible anti-inflammatory effects and mechanisms of Dioscorea nipponica Makino ethanol extract and its steroidal saponin dioscin. Our in vitro study shows that Dioscorea nipponica rhizome ethanol extract (DNRE) and dioscin protect against lipopolysaccharide (LPS)-activated inflammatory responses in BV-2 microglial cells by inhibiting phosphorylation and the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), resulting in the downregulation of pro-inflammatory cytokines and enzymes. Consistent with our previous report of dioscin-mediated enhancement of neurotrophic factors in dopaminergic cells, here we found that dioscin upregulates brain-derived neurotrophic factor (BDNF) and cAMP-response element binding protein (CREB) phosphorylation (pCREB) in the cerebral cortex and hippocampus regions of the mouse brain. Scopolamine treatment increased pro-inflammatory enzyme levels and reduced the expression of BDNF and pCREB in the hippocampus and cortex regions, which led to impaired learning and referencing memory in mice. Pre-treatment of dioscin for 7 days substantially enhanced mice performances in maze studies, indicating amelioration in cognitive deficits. In conclusion, DNRE and its active compound dioscin protect against neurotoxicity most likely by suppressing NF-κB phosphorylation and upregulating neurotrophic factor BDNF.
Mild cognitive impairment is a typical symptom of early Alzheimer’s disease (AD). Glehnia littoralis (G. littoralis), a medicinal halophyte plant commonly used to treat strokes, has been shown to ...possess some therapeutic qualities. In this study, we investigated the neuroprotective and anti-neuroinflammatory effects of a 50% ethanol extract of G. littoralis (GLE) on lipopolysccharide (LPS)-stimulated BV-2 cells and scopolamine-induced amnesic mice. In the in vitro study, GLE treatment (100, 200, and 400 µg/mL) markedly attenuated the translocation of NF-κB to the nucleus concomitantly with the significant mitigation of the LPS-induced production of inflammatory mediators, including NO, iNOS, COX-2, IL-6, and TNF-α. In addition, the GLE treatment suppressed the phosphorylation of MAPK signaling in the LPS-stimulated BV-2 cells. In the in vivo study, mice were orally administered with the GLE (50, 100, and 200 mg/kg) for 14 days, and cognitive loss was induced via the intraperitoneal injection of scopolamine (1 mg/kg) from 8 to 14 days. We found that GLE treatment ameliorated memory impairment and simultaneously improved memory function in the scopolamine-induced amnesic mice. Correspondingly, GLE treatment significantly decreased the AChE level and upregulated the protein expression of neuroprotective markers, such as BDNF and CREB, as well as Nrf2/HO-1 and decreased the levels of iNOS and COX-2 in the hippocampus and cortex. Furthermore, GLE treatment attenuated the increased phosphorylation of NF-κB/MAPK signaling in the hippocampus and cortex. These results suggest that GLE has a potential neuroprotective activity that may ameliorate learning and memory impairment by regulating AChE activity, promoting CREB/BDNF signaling, and inhibiting NF-κB/MAPK signaling and neuroinflammation.
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•GLE can inhibit the over activation of BV-2 cells by reducing the release of NO and inflammatory factors.•GLE can play an anti-inflammatory role through MAPK/NF-κB signaling pathways induced by LPS.•GLE reversed memory impairment through enhancing BDNF/CREB expression in scopolamine-induced C57BL/6 mouse model.•GLE prevents oxidative stress by regulating Nrf-2/HO-1 expression in scopolamine-induced C57BL/6 mouse model.
(Linn.) is a medicinal plant from China and Korea that has been traditionally used to control inflammation, to stop bedwetting and as a mouthwash in cases of bleeding gums. Its flowers are employed ...medicinally for their emollient, demulcent and diuretic properties, which make them useful in chest complaints. Furthermore, a flower extract decoction is used to improve blood circulation, for the treatment of constipation, dysmenorrhoea, haemorrhages, etc. However, the possible mechanisms of the immune-stimulatory effect remains to be elucidated. Therefore, we investigated the role of
flower (ARF) extracts in the immune-stimulatory effect of macrophages and the underlying mechanisms of action. ARF water extract (ARFW) could dose-dependently increase NO production and cytokines (IL-6 and TNF-α). We also found that ARFW significantly increased the expression of iNOS and COX-2 proteins in RAW264.7 cells. Consistent with these results, MAPK protein (JNK, ERK, p38) expression levels were induced after treatment with ARFW. Additionally, ARFW showed a marked increase in the phosphorylation level of IκBα and subsequent IκBα degradation allowing NF-κB nuclear translocation. These results suggest that the immune-stimulatory effect of
flower extracts is mediated through the translocation of NF-κB p65 subunit into the nucleus from the cytoplasm and subsequent activation of pro-inflammatory cytokines (IL-6 and TNF-α) and other mediators (iNOS and COX-2), which occurs mainly through MAPK signalling pathway. Thus, we suggest that ARFW could be considered as a potential therapeutic agent useful in the development of immune-stimulatory compounds.
Recent reports have shown the antidiabetic effect of Moringa oleifera from various parts of the world. However, M. oleifera from Cambodia has never determined. Therefore, the aim of this study was to ...assess the antidiabetic effect of M. oleifera extract from Cambodia. The leaf ethanolic extract contained flavonoids (31.90 mg/mL), polyphenols (53.03 mg/mL), lycopene (0.042 mg/mL), and ß-carotene (0.170 mg/mL), and possessed 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide, and hydroxyl radical scavenging activities of 92.40, 99.25, and 83.57 TE/μM at 1 mg/mL, respectively. Db/db mice were orally administered the leaf extract (150 mg/kg/day) for 5 weeks. M. oleifera treatment significantly ameliorated the altered fasting plasma glucose (from 483 to 312 mg/dL), triglyceride (from 42.12 to 23.00 mg/dL), and low-density lipoprotein cholesterol (from 107.21 to 64.25 mg/dL) compared to control group, and increased the insulin levels from 946 ± 92 to 1678 ± 268 pg/mL. The histopathological damage and expression levels of tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, cyclooxygenase-2, and inducible nitric oxide synthase in renal tissue decreased. These results indicate the potential antidiabetic benefits of M. oleifera ethanolic leaf extract.
Macrophages play a major role in innate immune responses by producing a variety of immune mediators and cytokines. The stimulation of macrophages by natural products may lead to an enhanced innate ...immune system. This study evaluated the immunostimulatory effects of a polysaccharide‐rich crude fraction of Celosia cristata L. flowers (CCP) on murine macrophages. CCP treatment induced the production of inducible nitric oxide synthase, cyclooxygenase‐2, and cytokines by macrophages. Mechanistically, the activation of mitogen‐activated protein kinases, NF‐κB and toll‐like receptor 4 were found to be associated with the stimulatory functions of CCP. CCP was found to be primarily composed of galacturonic acid and glucose in addition to small amounts of arabinose and galactose. This study demonstrated that CCP may enhance the innate immune responses and potentially improve the immune functions in the body.
The fruit of Chaenomeles sinensis has been traditionally used in ethnomedicine for the treatment of various human ailments, including pneumonia, bronchitis, and so on, but the pharmacological ...applications of the leaf part of the plant have not been studied. In this study, we evaluated the various radical scavenging activities and anti-inflammatory effects of different Chaenomeles sinensis leaf (CSL) extracts. The water extract showed a higher antioxidant and radical scavenging activities. However the ethanolic extracts showed higher NO scavenging activity than water extract, therefore the ethanolic extract of CSL was examined for anti-inflammatory effects on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The 70% ethanol extract of CSL (CSLE) has higher anti-inflammatory activity and significantly inhibited the production of nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). In addition, CSLE suppressed LPS-stimulated inducible nitric oxide synthase (iNOS) and NO production, IL-1β and phospho-STAT1 expression. In this study, we investigated the effect of CSLE on the production of inflammatory mediators through the inhibition of the TRIF-dependent pathways. Furthermore, we evaluated the role of CSLE on LPS-induced expression of pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6. Our results suggest that CSLE attenuates the LPS-stimulated inflammatory responses in macrophages through regulating the key inflammatory mechanisms, providing scientific support for its traditional uses in treating various inflammatory diseases.
Various biological effects have been reported for sulfated chitosan oligosaccharides, but the molecular mechanisms of action of their anti-inflammatory effects are still unknown. This study aimed to ...evaluate the anti-inflammatory effects of sulfated chitosan oligosaccharides and to elucidate the possible mechanisms of action. The results showed that pretreated low molecular weight sulfated chitosan oligosaccharides inhibited the production of nitric oxide (NO) and inflammatory cytokines such as IL-6 and TNF-α in lipopolysaccharide (LPS)-activated RAW264.7 cells. The sulfated chitosan oligosaccharides also suppressed inducible nitric oxide synthase (iNOS), phosphorylation of JNK and translocation of p65, a subunit of NF-κB, into the nucleus by inhibiting degradation of IκB-α. Our investigation suggests sulfated chitosan oligosaccharides inhibit IL-6/TNF-α in LPS-induced macrophages, regulated by mitogen-activated protein kinases (MAPKs) pathways dependent on NF-κB activation.
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